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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: 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.

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:

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.