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The number of studies that have been conducted on the possible benefits of different types of fasting or calorie restriction on cancer therapy, including the likelihood that these treatments lessen side effects, has been limited. However, the results are nevertheless promising. Chemotherapy’s adverse effects have led to a quest for options that reduce reliance on it. The susceptibility of tumorous cells to specific metabolites and nutrient deficiency is increasingly recognized as a key characteristic of the disease. This review delves into the data on various fasting methods and calorie restriction in rodents and humans, with a focus on biological adaptations that could potentially lower cancer risk or enhance cancer treatment results. We also emphasize recent scientific developments regarding the use of prolonged fasting and fasting-mimicking diets as a possible additional treatment for patients receiving immunotherapy or other treatments. This approach shows promise in enhancing treatment effectiveness, preventing resistance, and minimizing side effects. This study proposes that combining fasting and calorie restriction with chemotherapy, immunotherapy, or other therapies might be a potential technique to improve treatment efficacy, avoid resistance, and reduce adverse effects.

One of the biggest causes of death worldwide is cancer, which poses a serious threat to healthcare systems all over the world. Triple-negative breast cancer (TNBC), in particular, presents substantial clinical challenges because it does not express Human Epidermal Growth Factor Receptor 2 (HER2) or hormone receptors. Despite concerns about early recurrence and drug resistance, chemotherapy, particularly anthracyclines like Doxorubicin (DOX), remains the mainstay of treatment for TNBC patients. This research investigates the possibility of using natural products, especially piperine (PIP) and resveratrol (RES), to overcome DOX resistance. PIP and RES have shown anticancer effects via various pathways, such as inducing apoptosis and controlling the cell cycle. In this research, in vitro experiments showed that RES and PIP inhibit cell growth in a dose-dependent manner using triple-negative parent mouse mammary breast cancer cells and DOX resistance cells (EMT-6/P and EMT-6/DOX). RES in EMT-6/P cells showed an IC50 value of 146.511 ± 5.35 μM, and in EMT-6/DOX cells, it was 88.635 ± 29.507 μM. In the same way, PIP was found to have IC50 values of 148.819 ± 14.317 and 9.375 μM in the triplicate trials in EMT-6/P and EMT-6/DOX, respectively. Furthermore, on both cell lines, the combination demonstrated very strong synergistic effects; noticeably lower doses were needed for the combined treatment to reduce cell viability by 50%. The IC50 values for the combination treatments of RES and PIP were found to be < 2.289 µM and < 2.325 µM in EMT-6/P cells, respectively, with values < 0.348 µM and 0.243 ± 0.142 µM in EMT-6/DOX cells. The in vivo experiment conducted on Balb/C females indicated that mice bearing EMT-6/Dox cells and treated with the combination of RES and PIP had the highest cure percentage; however, this treatment showed mild toxicity. The study clarifies the potential synergistic activity between PIP and RES in combating DOX-resistant TNBC cells. These findings highlight the significance of investigating natural products as supplemental therapies in cancer treatment and provide insights into new treatment approaches. While the combination shows promise as a therapeutic option for treating breast cancer, especially in cases of DOX resistance, further investigation is needed.

Background: Angiotensin-converting enzyme 2 (ACE2) is a pivotal molecular nexus linking novel coronavirus disease to breast cancer. In-silico investigations have repurposed carnosine for both these conditions based on its potential ACE2 inhibitory properties. Methods: Utilizing an ACE2 inhibitor screening kit, we determined the inhibitory range of carnosine doses. Subsequently, we examined the effect of carnosine on ACE2 expression in supernatants from various breast cancer cell lines (MCF-7, MDA-MB-231, and EMT-6). Additionally, we compared ACE2 activity in cell line pellets with and without carnosine and a putative ACE2 activator using a fluorometric activity assay kit. Finally, we performed a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay across overlapping concentrations. Results: Carnosine exhibited dose-dependent ACE2 inhibition within the 100–300 mM range. ACE2 expression significantly diminished after exposure to carnosine for 2 and 24 h in MDA-MB-231 and MCF-7 cell lines, respectively. MTT assay unveiled notable antiproliferative effects in MDA-MB-231 (50 % survival at approximately 265 mM) and EMT-6 cell lines (unquantifiable 50 % survival dose). Conversely, the MCF-7 cell line displayed a modest increase in proliferation (Effective concentration 50–186 mM, ∼40 % increased survival). Conclusion: This pioneering study delineates evident dose-dependent ACE2 inhibition by carnosine. Moreover, it unveils the modulatory impact of this ACE2 inhibitor in breast cancer cell lines. Carnosine demonstrated a significant antiproliferative effect on aggressive cell lines while sparing luminal cell lines from substantial toxic or proliferative effects.

Background: Breast cancer (BC) is considered the most diagnosed cancer among women globally. This is because of its high possibility of metastasis and high resistance to chemotherapy. Cisplatin is a platinum-based antitumor agent that is used to treat various types of cancer. However, the main obstacle to using this drug is drug resistance. Drug resistance is a cause of most relapses of cancer which eventually lead to death. Nowadays, combining natural products is a trend to overcome drug resistance. Thymoquinone (TQ) is a natural phytochemical that exists mainly in blackseed. It has been used in medicine for decades, especially as an anticancer agent. Silymarin is a milk thistle compound that exhibits anticancer, hepatoprotective, and neuroprotective activity. Hence, the combination of TQ and silymarin could be a probable solution to treat cancer and reduce chemoresistance. Methods: This study tested this combination on cisplatin-sensitive (EMT6/P) and cisplatin-resistant (EMT6/CPR) mouse mammary cell lines. Apoptotic and antiproliferative activity was assessed for TQ and silymarin in vitro using caspase-3 and [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide] (MTT) assays, respectively. An in vivo study was performed to evaluate the effect of TQ and silymarin combination in mice inoculated with EMT6/P and EMT6/CPR cells. The safety profile was also examined using creatinine and liver enzyme assays. Results: In vitro, the TQ and silymarin combination synergized in both cell lines. Also, this combination caused apoptosis induction at a higher rate than the single treatment in both cell lines. In vivo, TQ and silymarin combination resulted in a remarkable reduction in tumor size and enhanced the cure rate in mice implanted with EMT6/P and EMT6/CPR cell lines. According to the safety profile results, TQ and silymarin combination was safe. Conclusion: In conclusion, the combination of TQ and silymarin provides a promising solution in treating BC resistant to cisplatin by inducing apoptosis. Further studies are needed to define the exact anticancer mechanisms of this combination.

Background: Breast cancer is one of the primary causes of death in women worldwide. Yearly, a quarter of cancer cases in women are breast cancer. The problem is aggravated by the emergence of chemotherapeutic resistance. One of the practices to overcome this problem is using natural products along with chemotherapy. Epigallocatechin Gallate (EGCG) is the main efficient catechin in green tea. Baicalin is the main active chemical constituent of Scutellaria baicalensis. Both natural products have anti-cancer and improving resistance activities. Therefore, a combination of EGCG and baicalin may afford a possible way out to overcome chemotherapeutic resistance. Methods: EGCG and baicalin were tested on Vincristine-sensitive (EMT-6/P) and Vincristine-resistant (EMT-6/V) mouse mammary cell lines. Antiproliferative and apoptotic effects were assessed for EGCG, baicalin, their combination, and Vincristine in vitro using MTT and caspase-3 assays. An in vivo study was conducted to assess the effect of EGCG, baicalin, their combination, vincristine, vincristine along with the combination in both EMT-6/P and EMT-6/V mouse mammary cell lines. The safety profile was also considered using liver enzymes and creatinine assays. Results: in vitro, EGCG and baicalin had synergistic effects in both cell lines. The combination of baicalin and EGCG as 140 and 100 µM respectively, caused an apoptotic effect higher than the single treatment of baicalin 175 µM or EGCG 125 µM, in vincristine-resistant cell lines. In vivo, the combination along with vincristine significantly enhanced the reduction of tumour size in mice implanted with EMT-6/P and EMT-6/V cell lines. According to the safety profile, the combinations of EGCG and baicalin are safe. Conclusion: The combination of baicalin and EGCG can be optimistic in improving vincristine-resistant cells to treatments.

Abstract Probiotics are a mixture of beneficial live bacteria and/or yeasts that naturally exist in our bodies. Recently, numerous studies have focused on the immunostimulatory effects of single-species or killed multi-species probiotic conditioned mediums on macrophages. This study investigates the immunostimulatory effect of commercially available active, multi-species probiotic conditioned medium (CM) on RAW264.7 murine macrophages. The probiotic CM was prepared by culturing the commercially available probiotic in a cell-culture medium overnight at 37 °C, followed by centrifugation and filter-sterilization to be tested on macrophages. The immunostimulatory effect of different dilution percentages (50%, 75%, 100%) of CM was examined using the MTT assay, proinflammatory cytokine (tumor necrosis factor TNF-alpha) production in macrophages, migration, and phagocytosis assays. For all the examined CM ratios, the percentages of cell viability were > 80%. Regarding the migration scratch, TNF-alpha and phagocytosis assays, CM demonstrated a concentration-dependent immunostimulatory effect. However, the undiluted CM (100%) showed a significant (p-value

Medicinal plants have been used since ancient times and may even be considered the origin of modern medicine. Natural products are a potential source for drug discovery and development of cancer treatments. Several pharmacological therapeutic activities were reported for Chiliadenus iphionoides. This research was designed to evaluate the essential oil of Chiliadenus iphionoides antioxidant potential and antiproliferative activity both in vitro and in vivo. The essential oil of Chiliadenus iphionoides was extracted by hydrodistillation. The chemical composition analysis was performed using gas chromatography. The main compounds identified in Chiliadenus iphionoides essential oil were oxygenated monoterpenes, such as eucalyptol (36.08%). A dose-dependent inhibition of cell proliferation was observed after the treatment of various cell lines (A549 (human lung cancer adenocarcinoma), MDA-MB-231 (triple-negative breast cancer cell line), T47 (human breast cancer cell line), EMT6/P (mouse mammary sarcoma cell line)) with increasing concentrations of the essential oil (0.02–2.5 mg/mL). The essential oil of Chiliadenus iphionoides was more cytotoxic against EMT6 and T47 cells with IC₅₀ values of 0.03±0.03 and 0.08± 0.009 mg/mL, respectively. The essential oil exhibited low cytotoxicity against a normal VERO cell line (IC₅₀ value > 4 mg/ml). Balb/C mice were inoculated with EMT6/p breast cancer cells and then treated with (60 mg/kg/day intraperitoneal injection) of essential extract for ten days. Interestingly, a significant (p < 0.05) reduction occurred in the tumor size of the treated group compared to the control group. Treatment toxicity was evaluated by measuring liver and kidney parameters. The tumor-bearing mice treated with the Chiliadenus iphionoides extract showed normal serum levels of AST, creatinine, and slight elevation in ALT level. The results indicated that Chiliadenus iphionoides have anticancer properties both in vitro and in vivo. We suggest that eucalyptol, a major active component, is a promising candidate for use as an anticancer agent. However, further molecular investigation is required to understand the molecular bearings of Chiliadenus iphionoides activity.

Cancer, a formidable disease with a significant mortality rate, continues to claim the lives of thousands of individuals annually in contemporary society. Conventional cancer therapies are notorious for their substantial adverse effects and lack of specificity. Within the context of neoplastic development, cancer hallmarks represent fundamental biological properties that cancer cells progressively acquire. A promising approach for combating cancer involves the simultaneous targeting of multiple cancer hallmarks. Plant-derived natural compounds stand out as a promising reservoir for the development of novel and more efficacious anticancer therapeutics due to their structural diversity and minimal toxicity profiles. Garlic (Allium sativum) has garnered considerable attention for its established anti-cancer properties over the years. Within garlic, a myriad of bioactive constituents, including organosulfur compounds, flavonoids, and phenolic compounds, exhibit distinct effects on cancer cells. The objective of this review paper is to furnish a comprehensive elucidation of the mechanisms underpinning the anticancer actions of garlic. The elucidated findings from the studies encompassed within this review not only contribute to a more profound comprehension of the anti-cancer properties of garlic but also serve as a robust foundation upon which researchers and healthcare practitioners can formulate enhanced anticancer pharmaceuticals grounded in natural garlic compounds.

Ligustrum ovalifolium (family Oleaceae) is a flowering plant with reported anti-inflammatory, antioxidant, hypotensive, and hypoglycemic activities. The present study investigated the phytochemical components and biological activities of L. ovalifolium leaves. Results showed that ethyl acetate extract has the highest potential to reduce cell growth in HeLa, T47D, and MDA-MB-231 cell lines with IC₅₀ values of 0.047, 0.07, and 0.072 mg/mL, respectively. Based on the LD50 value, the tumor-bearing mice were IP injected with 12.5 mg/kg of ethyl acetate extract. Tumor growth was significantly reduced (-43.1%) compared to the control group. According to the LC-MS analysis, Apigenin-7-O-glucoside was the flavonoid with the highest percentage value in L. ovalifolium leaves. DPPH assay exhibited antioxidant activity of ethanol and water extracts with the percentage of scavenging around 91% at a concentration of 200 µg/mL. As well, the assessment of liver and kidney functions of the experimented animals showed no toxicity effect compared to the control result. All things considered, the outcomes of this study revealed an antitumor potential of L. ovalifolium leaves extracts, hence this activity may arise from the presence of different potent flavonoids and the antioxidant potential. Nevertheless, further investigations are needed to determine the targets and signaling pathways that are affected by L. ovalifolium leaves extracts.

Breast cancer (BC) is the most prevalent malignancy in women and the first tumor type in the world. Ketogenic diets (KD), which are high in fat, low in carbohydrates, and sufficient in protein, can be used alone or as adjuvants with cancer drug medication as cancer therapy or prevention methods. Probiotics are nonpathogenic microorganisms or groups of bacteria that live in the gut and nourish the host body. In this work, we tested a new KD-probiotic combination against breast cancer implanted in mice. Several combination of probiotics (1×109 CFU/0.5ml) and KD (14.1 kcal/2g) reduced tumor size and enhanced cure rate. KD and combination therapy groups increased beta-hydroxybutyrate (β-OHB) while decrease blood glucose, and IGF-1.IFN-γ, IL-2, IL-4, and IL-10 serum levels were measured to assess immune reaction to various therapies. Combination and probiotics therapy raised IFN-γ, and IL-4 levels, however IL-10 level did decrease in all treated group with highest decrease in combination group. In the safety profile, probiotics, ketogenic diet, and their combination were safe. Overall, the combination of a ketogenic diet and probiotics has the potential to be utilized in the future development of anti-cancer nutrition to augment conventional therapies. Graphical abstract. Summary of the effect of Ketogenic diet, Probiotics and its combination on EMP-6 breast cancer cell and in vivo:

Cancer continues to be a prominent issue in healthcare systems, resulting in approximately 9.9 million fatalities in 2020. It is the second most common cause of death after cardiovascular diseases. Although there are difficulties in treating cancer at both the genetic and phenotypic levels, many cancer patients seek supplementary and alternative medicines to cope with their illness, relieve symptoms, and reduce the side effects of cytotoxic drug therapy. Consequently, there is an increasing emphasis on studying natural products that have the potential to prevent or treat cancer. Cancer cells depend on multiple hallmarks to secure survival. These hallmarks include sustained proliferation, apoptosis inactivation, stimulation of angiogenesis, immune evasion, and altered metabolism. Several natural products from food were reported to target multiple cancer hallmarks and can be used as adjuvant interventions to augment conventional therapies. This review summarizes the main active ingredients in food that have anticancer activities with a comprehensive discussion of the mechanisms of action. Thymoquinone, allicin, resveratrol, parthenolide, Epigallocatechin gallate, and piperine are promising anticancer bioactive ingredients in food. Natural products discussed in this review provide a solid ground for researchers to provide effective anticancer functional food.

Cancer, a leading global cause of mortality, arises from intricate interactions between genetic and environmental factors, fueling uncontrolled cell growth. Amidst existing treatment limitations, vitamins have emerged as promising candidates for cancer prevention and treatment. This review focuses on Vitamins A, C, E, and D because of their protective activity against various types of cancer. They are essential as human metabolic coenzymes. Through a critical exploration of preclinical and clinical studies via PubMed and Google Scholar, the impact of these vitamins on cancer therapy was analyzed, unraveling their complicated mechanisms of action. Interestingly, vitamins impact immune function, antioxidant defense, inflammation, and epigenetic regulation, potentially enhancing outcomes by influencing cell behavior and countering stress and DNA damage. Encouraging clinical trial results have been observed; however, further well-controlled studies are imperative to validate their effectiveness, determine optimal dosages, and formulate comprehensive cancer prevention and treatment strategies. Personalized supplementation strategies, informed by medical expertise, are pivotal for optimal outcomes in both clinical and preclinical contexts. Nevertheless, conclusive evidence regarding the efficacy of vitamins in cancer prevention and treatment is still pending, urging further research and exploration in this compelling area of study.

Background: Aescin is a mixture of the triterpene saponins extracted from the seeds of the horse chestnut tree Aesculus hippocastanum. Aescin has a venotonic, anti-inflammatory, antioxidant and anti-edematous characteristics that are mostly connected to the agent molecular mechanism. Objective: The present study aim to investigate the potential effects of Aescin on psoriasis induced by Imiquimod in male rats, ncluding its effect on the level of tumor necrosis factor alpha, Ki-67 and the histopathologic features of the psoriatic skin. Methods: Thirty-six albino male rats were divided into six groups each group containing 6 animals, psoriasis was induced by Imiquimod to five of the groups, while for the last group vasaline was applied and the group served as a control group. The animals were then treated with topical Aescin, topical clobetasol, combination of topical Aescin and clobetasol and oral Aescin, finally all animals were sacrificed and the dorsal back skin was taken to perform histopathological and immunohistochemical analysis. Results: regarding the level of Ki-67, Strong expression of Ki-67 was seen in the group who received Imiquimod only, where the scoring of Ki-67 was notably lowered among the other groups. However, the lowest expression was noticed in the group that were treated with the combination of topical Aescin and clobetasol. While the number of TNF-α positive cells and the intensity of immunostaining were higher in the induction group who received Imiquimod only and the lowest among the group who received the combination of topical Aescin and Clobetasol. Lastly the histopathologic analysis shows that the histopathologic features of psoriasis was markedly affected by the anti-inflammatory effect of Aescin and clobetasol, which was noticed through inhibition of proinflammatory markers, and the decrease in capillary permeability. Conclusion: Topical Aescin alone or in combination with clobetasol reduced Ki-67 expression successfully; furthermore, the combination of topical Aescin and Clobetasol decreased TNF- score and had the strongest anti-inflammatory activity more than the other groups. Lastly Aescin was able to alter the histopathologic features of the psoriatic skin through its anti-inflammatory, venotonic and anti-edematous activity.

Natural products, particularly medicinal plants, are crucial in combating cancer and aiding in the discovery and development of new therapeutic agents owing to their biologically active compounds. They offer a promising avenue for developing effective anticancer medications because of their low toxicity, diverse chemical structures, and ability to target various cancers. Allicin is one of the main ingredients in garlic (Allium sativum L.). It is a bioactive sulfur compound maintained in various plant sections in a precursor state. Numerous studies have documented the positive health benefits of this natural compound on many chronic conditions, including gastric, hepatic, breast, lung, cervical, prostate, and colon cancer. Moreover, allicin may target several cancer hallmarks or fundamental biological traits and functions that influence cancer development and spread. Cancer hallmarks include sustained proliferation, evasion of growth suppressors, metastasis, replicative immortality, angiogenesis, resistance to cell death, altered cellular energetics, and immune evasion. The findings of this review should provide researchers and medical professionals with a solid basis to support fundamental and clinical investigations of allicin as a prospective anticancer drug. This review outlines the anticancer role of allicin in each hallmark of cancer.

Epigallocatechin gallate (EGCG) is a catechin, which is a type of flavonoid found in high concentrations in green tea. EGCG has been studied extensively for its potential health benefits, particularly in cancer. EGCG has been found to exhibit anti-proliferative, anti-angiogenic, and pro-apoptotic effects in numerous cancer cell lines and animal models. EGCG has demonstrated the ability to interrupt various signaling pathways associated with cellular proliferation and division in different cancer types. EGCG anticancer activity is mediated by interfering with various cancer hallmarks. This article summarize and highlight the effects of EGCG on cancer hallmarks and focused on the impacts of EGCG on these cancer-related hallmarks. The studies discussed in this review enrich the understanding of EGCG’s potential as a therapeutic tool against cancer, offering a substantial foundation for scientists and medical experts to advance scientific and clinical investigations regarding EGCG’s possibility as a potential anticancer treatment.

Background: Chronic exposure to cigarette smoke produces neuroinflammation and long-term changes in neurotransmitter systems, especially glutamatergic systems.Objective: We examined the effects of cigarette smoke on astroglial glutamate transporters as well as NF-κB expression in mesocorticolimbic brain regions, prefrontal cortex (PFC) and nucleus accumbens (NAc). The behavioral consequences of cigarette smoke exposure were assessed using open field (OF) and light/dark (LD) tests to assess withdrawal-induced anxiety-like behavior.Methods: Sprague-Dawley rats were randomly assigned to five experimental groups: a control group exposed only to standard room air, a cigarette smoke exposed group treated with saline vehicle, two cigarette smoke exposed groups treated with acetylsalicylic acid (ASA) (15 mg/kg and 30 mg/kg, respectively), and a group treated only with ASA (30 mg/kg). Cigarette smoke exposure was performed for 2 h/day, 5 days/week, for 31 days. Behavioral tests were conducted weekly, 24 h after cigarette smoke exposure, during acute withdrawal. At the end of week 4, rats were given either saline or ASA 45 min before cigarette exposure for 11 days.Results: Cigarette smoke increased withdrawal-induced anxiety, and 30 mg/kg ASA attenuated this effect. Cigarette smoke exposure increased the relative mRNA and protein expression of nuclear factor ĸB (NFĸB) in PFC and NAc, and ASA treatment reversed this effect. Also, cigarette smoke decreased the relative mRNA and protein expression of glutamate transporter1 (GLT-1) and the cystine-glutamate transporter (xCT) in the PFC and the NAc, while ASA treatment normalized their expression.Conclusion: Cigarette smoke caused neuroinflammation, alterations in glutamate transporter expression, and increased anxiety-like behavior, and these effects were attenuated by acetylsalicylic acid treatment.

Breast cancer stands out as a particularly challenging form of cancer to treat among various types. Traditional treatment methods have been longstanding approaches, yet their efficacy has diminished over time owing to heightened toxicity, adverse effects, and the emergence of multi-drug resistance. Nevertheless, a viable solution has emerged through the adoption of a complementary treatment strategy utilizing natural substances and the incorporation of intermittent fasting to enhance therapeutic outcomes. This study aimed to assess the anticancer activity of thymoquinone (TQ), intermittent fasting, and their combination using in vivo and in vitro methods. The anti-proliferative activity of TQ and fasting (glucose/serum restriction) were evaluated against the T47D, MDA-MB-231, and EMT6 cell lines and compared to normal cell lines (Vero) using the MTT colorimetric assay method. Additionally, this study aimed to determine the half-maximal inhibitory concentration (IC50) of TQ. For the in vivo experiment, the antitumor activity of TQ and intermittent fasting (IF) was assessed by measuring the tumor sizes using a digital caliper to determine the change in the tumor size and survival rates. At the molecular level, the serum levels of glucose, β-hydroxybutyrate (β-HB), leptin, and insulin growth factor-1 (IGF-1) were measured using standard kits. Additionally, the aspartate transaminase (AST), alanine transaminase (ALT), and creatinine serum levels were measured. The inhibition of the breast cancer cell lines was achieved by TQ. TQ and intermittent fasting both had an additional anticancer effect against breast tumors inoculated in mice. The combination therapy was evaluated and found to significantly reduce the tumor size, with a change in tumor size of −57.7%. Additionally, the combination of TQ and IF led to a decrease in the serum levels of glucose, IGF-1 (24.49 ng/mL) and leptin (1.77 ng/mL) while increasing β-hydroxybutyrate in the mice given combination therapy (200.86 nM) with no toxicity on the liver or kidneys. In the mice receiving combination therapy, TQ and IF treated breast cancer in an additive way without causing liver or kidney toxicity due to decreased levels of glucose, IGF-1, and leptin and increased levels of β-hydroxybutyrate. Further investigation is required to optimize the doses and determine the other possible mechanisms exhibited by the novel combination.

Carthamus oxyacantha M.Bieb is a promising repository of active phytochemicals. These bioactive compounds work synergistically to promote the plant’s antioxidant, anticancer, and immunomodulatory capabilities. The present study aimed to discover the potential immunomodulatory and cytotoxicity of different extracts of Carthamus oxycantha roots. Aqueous ethanol (70%), aqueous methanol (90%), ethyl acetate, and n-hexane extracts were tested against five cell lines (T47D, MDA-MB231, Caco-2, EMT6/P, and Vero). Among these extracts, ethyl acetate and n-hexane extracts showed significant activity in inhibiting the proliferation of cancerous cells because of the presence of several phytochemical compounds, including flavonoids, phenolics, and alkaloids. The n-hexane extract was the most potent extract against T47D and Caco-2 cell lines and had IC50 values of 0.067 mg/mL and 0.067 mg/mL, respectively. In comparison, ethyl acetate extract was active against T47D and MDAMB231, and IC50 values were 0.0179 mg/mL and 0.03 mg/mL, respectively. Both n-hexane and ethyl acetate extracts reduced tumor size (by 49.981% and 51.028%, respectively). Remarkably, Carthamus oxyacantha extracts decreased the average weight of the tumor cells in the in vivo model. The plant induced significant apoptotic activity by the activation of caspase-3, immunomodulation of macrophages, and triggering of pinocytosis. The implications of these intriguing findings demand additional research to broaden the scope of the understanding of this field, opening the doors to the possibilities of using Carthamus oxyacantha M.Bieb as an effective cancer treatment adjuvant in the future.

Ethanol crude extract and four solvent fractions were extracted from M. autumnalis leave to evaluate their anticancer effect in both models: in vitro and in vivo. The in vitro assessments were conducted using the MTT method in five cancer cell lines and one normal cell line. Ethanol extract and n-hexane fraction showed antitumor activity against MCF-7 breast cancer cells with IC₅₀ values of 0.1 and 0.4 mg/ml, respectively, and low cytotoxicity against normal VERO cell line (IC₅₀ value > 4 mg/ml). Furthermore, expression levels of VEGF were tested in MCF-7 cells treated with M. autumnalis using Human VEGF Simple Step ELISA Kit. The results indicated downregulation of VEGF expression in the treated cells compared to the control group. Additionally, the LD₅₀ of M. autumnalis ethanol extract was calculated by applying an acute toxicity assay. Balb/C mice were inoculated with EMT6/p breast cancer cells and then treated with (137 mg/kg/day intraperitoneal injection) of ethanol extract for ten days. Interestingly, a significant (p < 0.001) reduction occurred in the tumor size of the treated group comparing to the control. Treatment in vivo toxicity was evaluated by measuring liver and kidney parameters. The tumor-bearing mice treated with the M. autumnalis extract showed normal serum level of AST, ALT, and creatinine. The results indicate that M. autumnalis has antitumor properties in both models in vitro and in vivo. However, further molecular investigation is required to understand the molecular bearings of M. autumnalis’ activity.

Cancer cells arise and grow in tumor microenvironment which consists of stromal cells and extracellular matrix. The dynamic interaction between cancer cells and different components of the tumor microenvironment is a critical step in cancer development and progression. Several therapeutic strategies were explored as promising approaches to target tumor microenvironment.Flavonoids have gained increasing importance in cancer therapy due to their high bioavailability, low toxicity, and affordability. Many flavonoids showed potent activities as potential cytotoxic agents and multiple nano- formulations were tested to enhance the therapeutic effect of flavonoids.In this review, a comprehensive analysis of flavonoid-based nanomedicine was provided with special emphasis on tumor microenvironment components as therapeutic targets. Studies discussed in this review provide a solid ground for researchers and physicians to consider flavonoid based nano- formulations as possible adjuvant therapies with conventional anticancer agents.

Although cancer is still one of the most significant global challenges facing public health, the world still lacks complementary approaches that would significantly enhance the efficacy of standard anticancer therapies. One of the essential strategies during cancer treatment is following a healthy diet program. The ketogenic diet (KD) has recently emerged as a metabolic therapy in cancer treatment, targeting cancer cell metabolism rather than a conventional dietary approach. The ketogenic diet (KD), a high-fat and very-low-carbohydrate with adequate amounts of protein, has shown antitumor effects by reducing energy supplies to cells. This low energy supply inhibits tumor growth, explaining the ketogenic diet’s therapeutic mechanisms in cancer treatment. This review highlights the crucial mechanisms that explain the ketogenic diet’s potential antitumor effects, which probably produces an unfavorable metabolic environment for cancer cells and can be used as a promising adjuvant in cancer therapy. Studies discussed in this review provide a solid background for researchers and physicians to design new combination therapies based on KD and conventional therapies.

Colorectal cancer (CRC) is the third most common cancer and the second most deadly cancer worldwide. Nevertheless, more than 70% of CRC cases are resulted from sporadic tumorigenesis and are not inherited. Since adenoma-carcinoma development is a slow process and may take up to 20 years, diet-based chemoprevention could be an effective approach in sporadic CRC. The Mediterranean diet is an example of a healthy diet pattern that consists of a combination of nutraceuticals that prevent several chronic diseases and cancer. Many epidemiological studies have shown the correlation between adherence to the Mediterranean diet and low incidence of CRC. The goal of this review is to shed the light on the anti-inflammatory and anti-colorectal cancer potentials of the natural bioactive compounds derived from the main foods in the Mediterranean diet.

Background: Antirrhinum majus (Snapdragon) is a perennial Mediterranean-native plant that is commonly used for mass display. Few reports acknowledged the traditional use of A. majus for its medicinal and therapeutic effects. Herein, we assess the impact of A. majus’s sample preparation and extraction methods on the plant-aerial parts’ phytochemical contents and antimicrobial activity. Furthermore, the microbial targets of the extracts’ secondary metabolites are inspected using molecular docking simulations. Methods: The leaves and flowers of A. majus were prepared as fresh and air-dried samples, then extracted using cold maceration and hot reflux, respectively. Extracts with the best phytochemical profiles were selected to test their antimicrobial activities against Bacillus subtilis, Staphylococcus aureus, Enterobacter aerogenes, Escherichia coli and Candida albicans. Besides, molecular docking of 66 reported isolated compounds was conducted against various microbial targets. Results: The dried-refluxed samples revealed a massive deterioration in their phytochemical profiles, whereas the macerated flowers extract exhibited the highest total phenolic content and antimicrobial activity against all tested bacterial strains. However, both flowers and leaves extracts showed similar minimum inhibitory and lethal concentrations against C. albicans. Molecular docking studies revealed that chlorogenic acid, chalcononaringenin 4’-glucoside, 3,4,2’,4’,6’-pentahydroxy-chalcone 4’-glucoside, apigenin-7-glucuronide, and luteolin-7-glucuronide were the lead compounds in expressing the antimicrobial activity. Yet, A. majus’s compounds could neither inhibit the 30S ribosomal subunit nor muramyl ligase E. Conclusion: Our results suggest that cold maceration of A. majus fresh aerial parts gave higher flavonoid and phenolic content contributing to its antimicrobial properties. These flavonoids and phenolic compounds are predicted to have a crucial role in inhibiting fungal sterol 14-demethylase, and bacterial dihydropteroate synthase and gyrase B subunit proteins.

Breast cancer is considered a universal public health dilemma in women. Due to the high toxicity and low selectivity of conventional anticancer therapies, there is a growing trend of using plant-derived natural products in cancer prevention and therapy. Ashwagandha (Withania somnifera, WS) has been used in the Mediterranean region and Ayurvedic medicine for millennia as a functional food and a medicinal plant with anticancer activity. Besides, intermittent fasting (IF) has been engaged recently in cancer treatment. Hence, the combination of WS and IF provides possible solutions to treat cancer and reduce chemoresistance when combined with chemotherapy. In this study, WS root (WSR), IF, and cisplatin were tested on cisplatin-sensitive (EMT6/P) and cisplatin-resistant (EMT6/CPR) mouse mammary cell lines. The phytochemical content of the WSR extract was analyzed using liquid chromatography–mass spectrometry (LC-MS) analysis. Antiproliferative and apoptotic effects were assessed for WSR extract, cisplatin, and their combination in vitro using [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide] (MTT) and caspase-3 assays. An in vivo study was used to assess the effect of WSR extract, IF, cisplatin, and their combinations in mice inculcated with EMT6/P and EMT6/CPR cells. The safety profile was also investigated using liver enzymes and creatinine assays. In vitro, WSR extract and cisplatin had a synergistic effect in both cell lines. The same combination induced an apoptotic effect higher than the single treatment in both cell lines. In vivo, several combinations of WSR extract, IF, or cisplatin caused significant tumor size reduction and improved the cure rate in mice implanted with EMT6/P and EMT6/CPR cell lines. IF-treated groups showed a significant reduction in serum glucose and an elevation in β-hydroxybutyrate (BHB) levels. In the safety profile, WSR extract, IF, and their combinations were safe. Overall, the combination of WSR extract and IF provides a promising solution for breast cancer treatment besides cisplatin by reducing the proliferation of cancer cells through induction of apoptosis. Moreover, they minimize cisplatin toxicity to the liver and kidney.

BackgroundFrom the earliest times, manna has been widely used as a tasty local sweet or folk medicine. The type of manna being investigated in the present study is called Gaz-alafi, a mixture of insect and Quercus brantii leaves secretions from oak forests in the north of Iraq and west of Iran.MethodsAqueous and ethanol extracts were prepared as decoction. Various phytochemical tests were conducted to analyze manna composition, including total phenolic contents using the Folin-Ciocalteu method and LC-MS. Gallic acid and catechin were detected in both extracts, in addition to tiliroside presence in ethanol extract, which added more value to the phenolic content of ethanol extract. Cytotoxic activities of Gaz alafi were evaluated against breast cancer cell lines and compared to normal cell lines and doxorubicin using the MTT assay. Antimicrobial properties were assessed against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus subtilis, and Candida albicans using the dilution method of the micro-titer plate. Serum levels of IFN-γ, interleukin-2 (IL-2), interleukin-4 (IL-4), and interleukin-10 (IL-10) were measured using ELISA. The effect of extracts on splenocyte proliferation was evaluated using the lymphocytes proliferation assay. Macrophage function was evaluated using the nitro blue tetrazolium assay, whereas pinocytosis was evaluated using the neutral red uptake assay. Ten days after tumor inoculation, changes in tumor size, survival rates, levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatinine were measured.ResultsThe growth of cancer cells was inhibited by Gaz alafi ethanol extract. An alteration in IFN- γ, IL-2, and IL-4 levels toward antiproliferation immune response were reported for both extracts. The aqueous extract efficiently stimulated lymphocyte proliferation, phagocytosis, and pinocytosis, followed by the ethanol extracts with moderate activity. After treating the mice with ethanol extracts, a significant reduction in tumor size and several undetected tumors were recorded.ConclusionsGaz alafi extracts (aqueous and ethanol) are promising sources for anticancer and immunostimulatory agents. Further studies are needed to fully identify the chemical composition of Gaz alafi extracts.

Cancer is one of the leading causes of death worldwide, with almost 10 million cancer-related deaths worldwide in 2020, so any investigation to prevent or cure this disease is very important. Spices have been studied widely in several countries to treat different diseases. However, studies that summarize the potential anticancer effect of spices used in Mediterranean diet are very limited. This review highlighted chemo-therapeutic and chemo-preventive effect of ginger, pepper, rosemary, turmeric, black cumin and clove. Moreover, the mechanisms of action for each one of them were figured out such as anti-angiogenesis, antioxidant, altering signaling pathways, induction of cell apoptosis, and cell cycle arrest, for several types of cancer. The most widely used spice in Mediterranean diet is black pepper (Piper nigrum L). Ginger and black cumin have the highest anticancer activity by targeting multiple cancer hallmarks. Apoptosis induction is the most common pathway activated by different spices in Mediterranean diet to inhibit cancer. Studies discussed in this review may help researchers to design and test new anticancer diets enriched with selected spices that have high activities.

The Mediterranean diet is regarded as one of the most healthful dietary patterns in the world, owing to a combination of foods high in antioxidants and anticancer constituents. Barley bran is one of the components of the Mediterranean diet. It has nutritional and beneficial effects in different pathological conditions. Many studies were achieved to assess the nutritious values of barley bran, but there is no research indicating immunomodulatory and anticancer activities of barley bran grown in Jordan. The present study aims to examine and assess the potential immunomodulatory and anti-tumor activities of ethanol, n-hexane, aqueous/methanol, and water extracts obtained from barley bran. The Maceration method was utilized to prepare ethanol, n-hexane, aqueous/methanol, and water extracts. Various phytochemical groups were determined by using qualitative phytochemical tests. The antiproliferative activity of extracts was determined against MCF-7, HCT-116, A549, and EMT6/p by the MTT assay. The Folin-Ciocalteu reagent was used to detect the total phenolic content in extracts. Furthermore, immunomodulatory activity was assessed by determining the effect of extracts on splenocytes proliferation in the presence and absence of mitogens. The nitro blue tetrazolium assay and the neutral red method were used to assess the effect of each extract on the phagocytic activity of macrophages and pinocytosis, respectively. For the in vivo part, three different concentrations (10, 20, and 30% w/v) of barley bran were used to test the prophylactic effect in four Balb/C mice groups inoculated with EMT6/p cell-line subcutaneously. Also, serum samples were collected to assess the effect on cytokines (IFN-gamma, IL-2, IL-4, and IL-10). Barley bran extracts inhibited cancer cell proliferation. According to immunoassays, n-hexane and aqueous/methanol extracts could significantly rise lymphocyte proliferation and pinocytosis activity of macrophages. The activity of phagocytosis was increased by n-hexane and ethanol extracts. For the in vivo part, the average tumor size and weight of mice given the 30% barley bran group was significantly reduced (p < 0.05) compared with the control group. During our study, higher levels of TH1 cytokines (IFN- γ, IL-2) and lower levels of TH2 cytokine (IL-4) and T regulatory cytokine (IL-10) were obtained due to consumption of barley bran in food. Barley bran can be used as a prophylactic agent because it has anti-cancer and immunomodulatory activities.

The Mediterranean diet includes the consumption of various fruits and vegetables. Lemon and ginger are highly popular in Mediterranean cuisine. The current study aims to evaluate both anticancer and immunomodulatory activities of lemon and ginger combination. The antiproliferative activities of the combination were tested against different cancer cell lines using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. The degree of apoptosis induction and vascular endothelial growth factor expression were detected using ELISA. Balb/C mice were inoculated with the EMT6/P breast cancer cells and received combination water extract orally for 14 days. The effect of the water extract on splenocytes proliferation was measured using the mitogen proliferation assay. Macrophage function was evaluated using the nitro blue tetrazolium assay and pinocytosis was assessed using the neutral red method. Gas chromatography coupled to the tandem mass spectrometry was used to determine the composition of the combination. The lemon and ginger combination showed significant apoptosis induction and angiogenesis suppression effects. Fifty percent of the mice taking this combination did not develop tumors with a percentage of tumor reduction of 32.8%. This combination showed a potent effect in stimulating pinocytosis. Alpha-pinene and α-terpineol were detected in high percentages in the combination water extract. The lemon and ginger combination represents promising options to develop anticancer infusions for augmenting conventional anticancer therapies. Further testing is required to understand the exact molecular mechanisms of this combination.

Emerging evidence supports the role of rice bran in cancer prevention. Studies were conducted on multiple rice cultivars. However, limited studies were conducted on rice cultivars in the Middle East. In this study, rice bran growing in Iraq (O. sativa ssp. Japonica, cultivars: Amber Barka) was evaluated for its effect on preventing cancer and stimulating the immune system. Rice bran was collected from local mills in Al-Najaf (south of Iraq). Several solvent extracts (ethanol, methanol, n-hexane, and water) were prepared by maceration. MTT assay was used to measure the antiproliferative effects of extracts against a panel of cancer cell lines. The ability of each extract to induce apoptosis and inhibit angiogenesis was measured using standard ELISA kits. The effect of extracts on the immune system was evaluated using a lymphocyte proliferation assay, a pinocytic activity assay, a phagocytic activity assay, and a Th1/Th2 cytokine detection kit. A microbroth dilution method was used to detect the antimicrobial activity of each extract against different microbial strains. LC–MS analysis was used to detect the phytochemical composition of extracts, while DPPH assay was used to determine the antioxidant activity. For the in vivo study, rice bran was added to mouse fodder at 10% and 20%. Mice were treated for two weeks using mouse fodder supplemented with rice bran. In the third week of the experiment, EMT6/P breast cancer cells (1 × 10⁶ cells/mL) were injected subcutaneously into the abdominal area of each mouse. The dimensions of the grown tumors were measured after 14 days of tumor inoculation. A microbroth dilution method was used to evaluate the antimicrobial activity of rice bran extracts against three bacterial strains. The highest antiproliferative activity was observed in ethanol and n-hexane extracts. Ethanol and methanol extract showed the highest activity to induce apoptosis and inhibit angiogenesis. Both extracts were also effective to enhance immunity by activating lymphocytes and phagocytes proliferation with modulations of cytokine levels. The incorporation of rice bran in mice food caused a 20% regression in tumor development and growth compared with the negative control. All extracts exhibited limited antimicrobial activity against tested microorganisms. Methanol extract showed antioxidant activity with an IC50 value of 114 µg/mL. LC–MS analysis revealed the presence of multiple phytochemicals in rice bran including apiin, ferulic acid, and succinic acid. Rice bran is a rich source of active phytochemicals that may inhibit cancer and stimulate the immune system. Rice bran’s biological activities could be due to the presence of multiple synergistically active phytochemicals. Further studies are needed to understand the exact mechanisms of action of rice bran.

Plants have been considered for many years as an important source of medicine to treat different diseases. Xanthium spinosum L. (Asteraceae, Compositae) is known for its diuretic, anti-inflammatory, and sedative effects. It is also used in the treatment of several ailments, such as cancer. In order to evaluate the anticancer and immunomodulatory activities, crude ethanol extract was prepared from the aerial part of X. spinosum and then fractionated using solvents with different polarities. As well, the chemical composition of X. spinosum extract and fractions were identified using LC-MS analysis. The antitumor effect of X. spinosum was assessed in both in vitro and in vivo models. Apoptosis induction was measured in vitro using a caspase-3 activity kit. Lymphocyte proliferation and phagocytosis and pinocytosis induction were used to quantify the effect of the plant extract and fractions on acquired and innate immunity, respectively. The effect of X. spinosum extract, and fractions on the levels of cytokines (IFN-γ, IL-2, IL-4, and IL-10) in murine lymphocytes was determined using a mouse-uncoated TH1/TH2 ELISA kit. Results showed that ethanol extract had the highest antiproliferative activity (IC₅₀ = 2.5 mg mL−1) against EMT6/P cell lines, while the aqueous and chloroform fractions had the highest apoptotic activity with 2.2 and 1.7 folds, respectively. On the other hand, the n-hexane fraction was the most effective in stimulating lymphocyte proliferation, whereas ethanol extract, aq. Methanol and aqueous fractions exhibited the highest phagocytic activity. As well, X. spinosum extract and fractions were able to modulate the expression of IL-2, IL-4, and IFN-γ. A remarkable decrease in tumor size was accomplished following the treatment of tumor-bearing mice with X. spinosum extract and fractions. Both aq. Methanol and chloroform fractions showed the highest percentage change in tumor size with -58 and -55%, respectively. As well, tumor-bearing mice treated with chloroform fraction demonstrated a high curable percentage with a value of 57.1%. Anyway, X. spinosum extract and fractions exhibited no toxic impact on the liver or kidney functions of the mice-treated groups. These findings may confirm that X. spinosum has favorable anticancer and immunomodulatory effects. However, additional studies are required to fully understand the mechanisms of action of this plant and the signaling pathways involved in its effects. Moreover, more testing is needed to have better insight into the apoptotic pathway and to know the exact concentration of active compounds.

Cancer is still one of the most widespread diseases globally, it is considered a vital health challenge worldwide and one of the main barriers to long life expectancy. Due to the potential toxicity and lack of selectivity of conventional chemotherapeutic agents, discovering alternative treatments is a top priority. Plant-derived natural products have high potential in cancer treatment due to their multiple mechanisms of action, diversity in structure, availability in nature, and relatively low toxicity. In this review, the anticancer mechanisms of the most common phytochemicals were analyzed. Furthermore, a detailed discussion of the anticancer effect of combinations consisting of natural product or natural products with chemotherapeutic drugs was provided. This review should provide a strong platform for researchers and clinicians to improve basic and clinical research in the development of alternative anticancer medicines.

Cancer is the second leading cause of death after cardiovascular diseases. Conventional anticancer therapies are associated with lack of selectivity and serious side effects. Cancer hallmarks are biological capabilities acquired by cancer cells during neoplastic transformation. Targeting multiple cancer hallmarks is a promising strategy to treat cancer. The diversity in chemical structure and the relatively low toxicity make plant-derived natural products a promising source for the development of new and more effective anticancer therapies that have the capacity to target multiple hallmarks in cancer. In this review, we discussed the anticancer activities of ten natural products extracted from plants. The majority of these products inhibit cancer by targeting multiple cancer hallmarks, and many of these chemicals have reached clinical applications. Studies discussed in this review provide a solid ground for researchers and physicians to design more effective combination anticancer therapies using plant-derived natural products.

Desert truffles have high nutritional value and grow wild in the Mediterranean basin and Western Asia. Although, many studies were performed to evaluate truffles nutritious values and phytochemical composition, studies are limited to evaluate their anticancer and/ or immunomodulatory effects. Our study was conducted to evaluate the anticancer and immunomodulatory effects of Terfezia boudieri (desert truffle). Different solvent extracts were prepared from the truffle and MTT assay was used to measure their anticancer activity against cancer cell lines (T47D, MCF-7, MDA-MB231, HCT-116, and Hela). Total phenolic content in each extract was determined by using Folin-Ciocalteu reagent and qualitative phytochemical screening was performed using standard methods. The degree of apoptosis induction (using caspase 3 assay) and vascular endothelial growth factor expression were detected using standard kits. Also, ELISA was used to measure levels of IFN-γ, IL-2, IL-4, and IL-10 secreted by splenocytes after treatment with the extracts. The effect of the extracts on splenocytes proliferation was measured using MTT assay. Macrophage function was evaluated using nitro blue tetrazolium assay and pinocytosis function was evaluated using neutral red method. Terpenoids, phytosterols, and carbohydrates were present in all the solvent extracts, while tannins, alkaloids and flavonoids were detected only in aqueous/methanol and aqueous extracts. The highest total phenolic content was observed in aqueous and aqueous methanol extracts. The growth of cancer cell lines was inhibited by T. boudieri extracts in a dose dependent manner. N-hexane extract was the most potent against most cell lines. Aqueous/methanol extract showed high apoptosis induction and angiogenesis suppression effects. An increase in TH1 cytokines (IFN-γ, IL-2) level and a decrease in TH2 cytokine (IL-4) level were evident after lymphocytes stimulation by aqueous/methanol, n-hexane and ethyl acetate extracts of T. boudieri. Ethyl acetate extract of T. boudieri were the most potent extracts to stimulate lymphocytes proliferation while all other extracts showed moderate stimulation. Aqueous/methanol extract was the most active extract to stimulate phagocytosis. Ethyl acetate extract was the most active extract to stimulate pinocytosis. The use of T. boudieri provides variable health benefits. N-hexane, ethyl acetate, and aqueous/methanol extracts exhibited anticancer activities and are potent stimulators of innate and acquired immunity. Further testing is needed to identify the biologically active compounds and detect them quantitatively using GC-MS analysis.

The objective of this research was to investigate the effect of polymer length on the in vitro characteristics of thymoquinone-melatonin (TQ-MLT) when loaded into our previously prepared targeted drug delivery system (TDDS). Our system constructed from silica nanoparticles (NPs) and modified with diamine polymer (D4000), carboxymethyl-β-cyclodextrin (CM-β-CD) and folic acid (FA), respectively. In this study, three other different lengths of polymers (D230, D400 and D2000) were used and compared to D4000. The surface modification was characterized using fourier transform infrared spectroscopy (FTIR) and the mean particle size as well as polydispersity (PD) was measured using dynamic light scattering (DLS). The results, in general, showed that the release rate increases as the polymer length decreases. Also, shorter polymers showed an obvious burst release of most of the drug within the first hour. On the other hand, longer polymers exhibited a more sustained release in a pulsatile manner, with two moderate drug burst patterns occurred within the first and the last few hours. The in vitro cell viability assay showed that the percentage of cell toxicity toward HeLa cells increases with increasing the polymer length. Keywords: Silica nanoparticles, Diamine polymers, Targeting, In vitro, Toxicity

Aloysia citrodora (Verbenaceae) is traditionally used to treat various diseases, including bronchitis, insomnia, anxiety, digestive, and heart problems. In this study, this plant’s antioxidant and anti-proliferation effects were evaluated. In addition to volatiles extraction, different solvent extracts were prepared. The GC-MS, LC-MS analysis and the Foline-Ciocalteu (F-C) method were used to investigate the phytochemical components of the plant. MTT assay was used to measure the antiproliferative ability for each extract. Antioxidant activity was determined using the 2,2-diphenylpicrylhydrazyl (DPPH) assay. In in vivo anti-proliferation experiments, Balb/C mice were inoculated with tumor cells and IP-injected with ethyl acetate extract of A. citrodora. After treatment, a significant reduction in tumor size (57.97%) and undetected tumors (44.44%) were obtained in treated mice, demonstrating the antiproliferative efficacy of the ethyl acetate extract. Besides, ethanol extract revealed the most potent radical scavenging effect. The findings of this study displayed that A. citrodora has promising cytotoxic and antioxidant activities. Still, further testing is required to investigate the extract’s chemical composition to understand its mechanisms of action.

Cancer is one of the leading causes of death globally. The development of drug resistance is the main contributor to cancer-related mortality. Cancer cells exploit multiple mechanisms to reduce the therapeutic effects of anticancer drugs, thereby causing chemotherapy failure. Natural products are accessible, inexpensive, and less toxic sources of chemotherapeutic agents. Additionally, they have multiple mechanisms of action to inhibit various targets involved in the development of drug resistance. In this review, we have summarized the basic research and clinical applications of natural products as possible inhibitors for drug resistance in cancer. The molecular targets and the mechanisms of action of each natural product are also explained. Diverse drug resistance biomarkers were sensitive to natural products. P-glycoprotein and breast cancer resistance protein can be targeted by a large number of natural products. On the other hand, protein kinase C and topoisomerases were less sensitive to most of the studied natural products. The studies discussed in this review will provide a solid ground for scientists to explore the possible use of natural products in combination anticancer therapies to overcome drug resistance by targeting multiple drug resistance mechanisms.

Cancer is considered the second leading cause of death worldwide and in 2018 it was responsible for approximately 9.6 million deaths. Globally, about one in six deaths are caused by cancer. A strong correlation was found between diabetes mellitus and carcinogenesis with the most evident correlation was with type 2 diabetes mellitus (T2DM). Research has proven that elevated blood glucose levels take part in cell proliferation and cancer cell progression. However, limited studies were conducted to evaluate the efficiency of conventional therapies in diabetic cancer patients. In this review, the correlation between cancer and diabetes will be discussed and the mechanisms by which the two diseases interact with each other, as well as the therapeutics challenges in treating patients with diabetes and cancer with possible solutions to overcome these challenges. Natural products targeting both diseases were discussed with detailed mechanisms of action. This review will provide a solid base for researchers and physicians to test natural products as adjuvant alternative therapies to treat cancer in diabetic patients.

Melatonin is a pleotropic molecule with numerous biological activities. Epidemiological and experimental studies have documented that melatonin could inhibit different types of cancer in vitro and in vivo. Results showed the involvement of melatonin in different anticancer mechanisms including apoptosis induction, cell proliferation inhibition, reduction in tumor growth and metastases, reduction in the side effects associated with chemotherapy and radiotherapy, decreasing drug resistance in cancer therapy, and augmentation of the therapeutic effects of conventional anticancer therapies. Clinical trials revealed that melatonin is an effective adjuvant drug to all conventional therapies. This review summarized melatonin biosynthesis, availability from natural sources, metabolism, bioavailability, anticancer mechanisms of melatonin, its use in clinical trials, and pharmaceutical formulation. Studies discussed in this review will provide a solid foundation for researchers and physicians to design and develop new therapies to treat and prevent cancer using melatonin.

Hyacinthus orientalis L. (family Hyacinthaceae) is traditionally used to treat different diseases including cancer. In this study, the anticancer and immunomodulatory effects of this plant were evaluated. Hydroalcoholic extract was prepared, and different solvent fractions were obtained using solvent–solvent extraction. In the anticancer part, MTT assay and caspase-3 ELISA kits were used to measure the antiproliferative and apoptosis induction ability for each extract, respectively. In the immunomodulatory part, lymphocyte proliferation assay and cytokines detection kit were used to measure the effect of extracts of acquired immunity. Phagocytosis and pinocytosis induction were used to evaluate the effect of extracts on the innate immunity. GC–MS, LC–MS, and Foline–Ciocalteu assays were used to identify the chemical composition of the plant. Balb/C mice were inoculated with breast cancer and treated with hydroalcoholic extract of H. orientalis L. Results showed that hydroalcoholic extract and n-hexane fraction were highly effective in apoptosis induction. Both extract and fraction were also effective in stimulating lymphocytes proliferation and phagocytosis. Significant reduction in tumor size was achieved after treating tumor-bearing mice with hydroalcoholic extract. Additionally, high cure percentages (50%) were obtained in treated mice. Results of this study showed that H. orientalis L. has promising anticancer and immunomodulatory activities. However, further studies are needed to explore more details of apoptosis induction ability and other mechanisms of action and to measure different signaling pathways responsible for the anticancer and immunomodulatory response.

Diabetes is a global health problem, and the number of diabetic patients is in continuous rise. Conventional antidiabetic therapies are associated with high costs and limited efficiency. The use of traditional medicine and plant extracts to treat diabetes is gaining high popularity in many countries. Countries in the Middle East region have a long history of using herbal medicine to treat different diseases, including diabetes. In this review, we compiled and summarized all the in vivo and in vitro studies conducted for plants with potential antidiabetic activity in the Middle East region. Plants of the Asteraceae and Lamiaceae families are the most investigated. It is hoped that this review will contribute scientifically to evidence the ethnobotanical use of medicinal plants as antidiabetic agents. Work has to be done to define tagetes, mechanism of action and the compound responsible for activity. In addition, safety and pharmacokinetic parameters should be investigated.

Cancer is one of the main causes of death globally and considered as a major challenge for the public health system. The high toxicity and the lack of selectivity of conventional anticancer therapies make the search for alternative treatments a priority. In this review, we describe the main plant-derived natural products used as anticancer agents. Natural sources, extraction methods, anticancer mechanisms, clinical studies, and pharmaceutical formulation are discussed in this review. Studies covered by this review should provide a solid foundation for researchers and physicians to enhance basic and clinical research on developing alternative anticancer therapies.

The release of reactive oxygen species (ROS) and oxidative stress is associated with the development of many ailments, including cardiovascular diseases, diabetes and cancer. The causal link between oxidative stress and cancer is well established and antioxidants are suggested as a protective mechanism against cancer development. Recently, an increase in the consumption of antioxidant supplements was observed globally. The main sources of these antioxidants include fruits, vegetables, and beverage. Herbal infusions are highly popular beverages consumed daily for different reasons. Studies showed the potent antioxidant effects of plants used in the preparation of some herbal infusions. Such herbal infusions represent an important source of antioxidants and can be used as a dietary protection against cancer. However, uncontrolled consumption of herbal infusions may cause toxicity and reduced antioxidant activity. In this review, eleven widely consumed herbal infusions were evaluated for their antioxidant capacities, anticancer potential and possible toxicity. These herbal infusions are highly popular and consumed as daily drinks in different countries. Studies discussed in this review will provide a solid ground for researchers to have better understanding of the use of herbal infusions to reduce oxidative stress and as protective supplements against cancer development.

Resveratrol (3,4′,5 trihydroxystilbene) is a naturally occurring non-flavonoid polyphenol. It has various pharmacological effects including antioxidant, anti-diabetic, anti-inflammatory and anti-cancer. Many studies have given special attention to different aspects of resveratrol anti-cancer properties and proved its high efficiency in targeting multiple cancer hallmarks. Tumor microenvironment has a critical role in cancer development and progression. Tumor cells coordinate with a cast of normal cells to aid the malignant behavior of cancer. Many cancer supporting players were detected in tumor microenvironment. These players include blood and lymphatic vessels, infiltrating immune cells, stromal fibroblasts and the extracellular matrix. Targeting tumor microenvironment components is a promising strategy in cancer therapy. Resveratrol with its diverse biological activities has the capacity to target tumor microenvironment by manipulating the function of many components surrounding cancer cells. This review summarizes the targets of resveratrol in tumor microenvironment and the mechanisms involved in this targeting. Studies discussed in this review will participate in building a solid ground for researchers to have more insight into the mechanism of action of resveratrol in tumor microenvironment.

Six Schiff bases were prepared by reacting 3,3′-diaminodipropylamine with different benzaldehyde derivatives. The structures of these compounds were confirmed through different spectroscopic methods such as 1H-NMR, 13C-NMR and mass spectrometry. The prepared compounds were evaluated in vitro for their antimicrobial activity against a number of pathogenic Gram-positive and Gram-negative bacteria and Candida by the twofold serial dilution method. These compounds showed bacteriostatic rather than bactericidal activities against Gram positive and Gram-negative bacteria. In addition, compound 3c exhibited significant anticandida activity with an MIC of 24 μg/ml and is, therefore, considered as a promising and potential antifungal agent; further modification can be done on the structure of the compound for a better drug candidate in the future.

Background: The effects of metformin (MET) and curcumin (CUR) single treatments have been tested against breast cancer; however, their combination has not been explored. Here, we evaluated the antitumor activity of MET and CUR combination against breast cancer in mice. Materials and methods: The antiproliferative activity of single and combined treatments against breast cancer cell lines was determined. Vascular endothelial growth factor (VEGF) and Trp53 expression was examined in EMT6/P cells. In vivo studies were carried out by inoculating BALB/c mice with EMT6/P cells and examining tumor growth and apoptosis induction in tumor sections. Furthermore, serum levels of different cytokines and transaminases and creatinine were measured to detect the immune response and toxicity, respectively. Results: The combination treatment exhibited the highest effects against tumor proliferation and growth. It significantly reduced VEGF expression, induced Trp53 independent apoptosis, triggered Th2 immune response and showed no toxicity. Conclusion: The combination can be a potential therapeutic option to treat breast cancer. However, further testing is needed to measure the exact serum levels of MET and CUR and to further explain the obtained results.