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Background: Dental pathogens play a crucial role in oral health issues, including tooth decay, gum disease, and oral infections, and recent research suggests a link between these pathogens and oral cancer initiation and progression. Innovative therapeutic approaches are needed due to antibiotic resistance concerns and treatment limitations., Methods: We synthesized and analyzed piperine-coated zinc oxide nanoparticles (ZnO-PIP NPs) using UV spectroscopy, SEM, XRD, FTIR, and EDAX. Antioxidant and antimicrobial effectiveness were evaluated through DPPH, ABTS, and MIC assays, while the anticancer properties were assessed on KB oral squamous carcinoma cells., Results: ZnO-PIP NPs exhibited significant antioxidant activity and a MIC of 50 µg/mL against dental pathogens, indicating strong antimicrobial properties. Interaction analysis revealed high binding affinity with dental pathogens. ZnO-PIP NPs showed dose-dependent anticancer activity on KB cells, upregulating apoptotic genes BCL2, BAX, and P53., Conclusions: This approach offers a multifaceted solution to combatting both oral infections and cancer, showcasing their potential for significant advancement in oral healthcare. It is essential to acknowledge potential limitations and challenges associated with the use of ZnO NPs in clinical applications. These may include concerns regarding nanoparticle toxicity, biocompatibility, and long-term safety. Further research and rigorous testing are warranted to address these issues and ensure the safe and effective translation of ZnO-PIP NPs into clinical practice., (© 2024. The Author(s).)

Spinal cord injury (SCI) is a neurological disorder associated with the loss of sensory and motor function. Understanding the precise dysregulated signaling pathways, especially apoptosis and autophagy following SCI, is of vital importance in developing innovative therapeutic targets and treatments. The present study lies in the fact that it reveals the precise dysregulated signaling mediators of apoptotic and autophagic pathways following SCI and also examines the effects of polyphenols and other candidate phytochemicals. It provides new insights to develop new treatments for post-SCI complications. Accordingly, a comprehensive review was conducted using electronic databases including, Scopus, Web of Science, PubMed, and Medline, along with the authors' expertise in apoptosis and autophagy as well as their knowledge about the effects of polyphenols and other phytochemicals on SCI pathogenesis. The primary mechanical injury to spinal cord is followed by a secondary cascade of apoptosis and autophagy that play critical roles during SCI. In terms of pharmacological mechanisms, caspases, Bax/Bcl-2, TNF-α, and JAK/STAT in apoptosis along with LC3 and Beclin-1 in autophagy have shown a close interconnection with the inflammatory pathways mainly glutamatergic, PI3K/Akt/mTOR, ERK/MAPK, and other cross-linked mediators. Besides, apoptotic pathways have been shown to regulate autophagy mediators and vice versa. Prevailing evidence has highlighted the importance of modulating these signaling mediators/pathways by polyphenols and other candidate phytochemicals post-SCI. The present review provides dysregulated signaling mediators and therapeutic targets of apoptotic and autophagic pathways following SCI, focusing on the modulatory effects of polyphenols and other potential phytochemical candidates., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Curcumin is a natural phytochemical polyphenol with significant anti-cancer effects and negligible side effects. In this study, the therapeutic capacity of nanomicellar-curcumin for treating lung metastasis was evaluated in an immunocompetent mouse model of metastatic melanoma., Martials and Methods: Two doses of nanomicellar-curcumin (i.e. 10 and 20 μM) were used to induce cytotoxicity in 3 melanoma cell lines. A total of 60 mice were allocated to 20 mice in each of three groups (10 for survival and 10 for assays). Groups were no treatment control, PBS control, nanomicellar-curcumin 20 mg/kg IP 4 times a week, for three weeks). Immunohistochemistry, TUNEL assay, and Western blots were used on lung samples., Results: Nanomicellar-curcumin inhibited the in vitro growth of B16 F10 melanoma cells at 20 μM over 72 h. In vivo, 20 mg/kg nanomicellar-curcumin injected IP, delayed tumor cell growth and significantly extended mouse survival rate. Tumor infiltration of regulatory T cells and angiogenesis were reduced, while IFN-γ and CXCL10 were increased., Conclusion: Nanomicellar-curcumin can inhibit lung metastasis and growing melanoma via activation of apoptosis, activated T cells and inhibition of angiogenesis, tumor growth and regulatory T cells., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Simple Summary: This review describes the anticancer activities of several marine peptides isolated from cyanobacteria and their specific effects against neuroblastoma. After a short presentation of the major cyanobacterial peptides of marine origin, mainly belonging to the cyclic depsipeptide family, this work has focused on the different mechanisms of action of these peptides (effects on apoptosis, cell cycle arrest, autophagy, sodium channel blocking as well as antimetastatic activities). A thorough description of the biological effects of the marine cyanobacterial marine peptides is developed including data on their half-maximal effective concentration (EC50), growth inhibition 50% (GI50) and lethal concentration 50 (LC50) on various neuroblastoma cell lines. This review ends with a description of the clinical trials which are underway to evaluate the anticancer effects of peptides arising from marine cyanobacteria and microalgae. Conclusions envisage the potential role of such peptides for the development of anti-neuroblastoma medicines and a platform for uncovering new therapeutic cellular targets. Neuroblastoma is the most prevalent extracranial solid tumor in pediatric patients, originating from sympathetic nervous system cells. Metastasis can be observed in approximately 70% of individuals after diagnosis, and the prognosis is poor. The current care methods used, which include surgical removal as well as radio and chemotherapy, are largely unsuccessful, with high mortality and relapse rates. Therefore, attempts have been made to incorporate natural compounds as new alternative treatments. Marine cyanobacteria are a key source of physiologically active metabolites, which have recently received attention owing to their anticancer potential. This review addresses cyanobacterial peptides' anticancer efficacy against neuroblastoma. Numerous prospective studies have been carried out with marine peptides for pharmaceutical development including in research for anticancer potential. Marine peptides possess several advantages over proteins or antibodies, including small size, simple manufacturing, cell membrane crossing capabilities, minimal drug–drug interactions, minimal changes in blood–brain barrier (BBB) integrity, selective targeting, chemical and biological diversities, and effects on liver and kidney functions. We discussed the significance of cyanobacterial peptides in generating cytotoxic effects and their potential to prevent cancer cell proliferation via apoptosis, the activation of caspases, cell cycle arrest, sodium channel blocking, autophagy, and anti-metastasis behavior. [ABSTRACT FROM AUTHOR]

Simple Summary: Over the years, alternative and complementary medicine have garnered much attention all across the globe. To this end, phytochemicals have intriguing potential against myriads of disease conditions; nevertheless, as of yet, the molecular intricacies for their therapeutic potential is incompletely understood. It is widely acknowledged that proteomics technology has been ex-plored as a reliable approach to understand the molecular intricacies related to phytochemi-cal-based therapeutic interventions. Reckoning with this, the present review provides an overview of the proteomics studies performed to unravel the underlying molecular intricacies of various phytochemicals such as Curcumin, Genistein, and Tanshinone IIA. Phytochemicals possess various intriguing pharmacological properties against diverse pathological conditions. Extensive studies are on-going to understand the structural/functional properties of phytochemicals as well as the molecular mechanisms of their therapeutic function against various disease conditions. Phytochemicals such as curcumin (Cur), genistein (Gen), and tanshinone-IIA (Tan IIA) have multifaceted therapeutic potentials and various efforts are in progress to understand the molecular dynamics of their function with different tools and technologies. Cur is an active lipophilic polyphenol with pleiotropic function, and it has been shown to possess various intriguing properties including antioxidant, anti-inflammatory, anti-microbial, anticancer, and anti-genotoxic properties besides others beneficial properties. Similarly, Gen (an isoflavone) exhibits a wide range of vital functions including antioxidant, anti-inflammatory, pro-apoptotic, anti-proliferative, anti-angiogenic activities etc. In addition, Tan IIA, a lipophilic compound, possesses antioxidant, anti-angiogenic, anti-inflammatory, anticancer activities, and so on. Over the last few decades, the field of proteomics has garnered great momentum mainly attributed to the recent advancement in mass spectrometry (MS) techniques. It is envisaged that the proteomics technology has considerably contributed to the biomedical research endeavors lately. Interestingly, they have also been explored as a reliable approach to understand the molecular intricacies related to phytochemical-based therapeutic interventions. The present review provides an overview of the proteomics studies performed to unravel the underlying molecular intricacies of various phytochemicals such as Cur, Gen, and Tan IIA. This in-depth study will help the researchers in better understanding of the pharmacological potential of the phytochemicals at the proteomics level. Certainly, this review will be highly instrumental in catalyzing the translational shift from phytochemical-based biomedical research to clinical practice in the near future. [ABSTRACT FROM AUTHOR]

Edible flowers are attracting special therapeutic attention and their administration is on the rise. Edible flowers play pivotal modulatory roles on oxidative stress and related interconnected apoptotic/inflammatory pathways toward the treatment of cancer. In this review, we highlighted the phytochemical content and therapeutic applications of edible flowers, as well as their modulatory potential on the oxidative stress pathways and apoptotic/inflammatory mediators, resulting in anticancer effects. Edible flowers are promising sources of phytochemicals (e.g., phenolic compounds, carotenoids, terpenoids) with several therapeutic effects. They possess anti-inflammatory, anti-diabetic, anti-microbial, anti-depressant, anxiolytic, anti-obesity, cardioprotective, and neuroprotective effects. Edible flowers potentially modulate oxidative stress by targeting erythroid nuclear transcription factor-2/extracellular signal-regulated kinase/mitogen-activated protein kinase (Nrf2/ERK/MAPK), reactive oxygen species (ROS), nitric oxide (NO), malondialdehyde (MDA) and antioxidant response elements (AREs). As the interconnected pathways to oxidative stress, inflammatory mediators, including tumor necrosis factor (TNF)-α, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), interleukins (ILs) as well as apoptotic pathways such as Bcl-2-associated X protein (Bax), Bcl-2, caspase and cytochrome C are critical targets of edible flowers in combating cancer. In this regard, edible flowers could play promising anticancer effects by targeting oxidative stress and downstream dysregulated pathways. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is the leading cause of cancer death in men, and its treatment is commonly associated with severe adverse effects. Thus, new treatment modalities are required. In this context, natural compounds have been widely explored for their anti-PCa properties. Aquatic organisms contain numerous potential medications. Anticancer peptides are less toxic to normal cells and provide an efficacious treatment approach via multiple mechanisms, including altered cell viability, apoptosis, cell migration/invasion, suppression of angiogenesis and microtubule balance disturbances. This review sheds light on marine peptides as efficacious and safe therapeutic agents for PCa. [ABSTRACT FROM AUTHOR]

Cancer is one of the leading causes of death and a great threat to people around the world. Cancer treatment modalities include surgery, radiotherapy, chemotherapy, radiochemotherapy, hormone therapy, and immunotherapy. The best approach is to use a combination of several types. Among the treatment methods mentioned above, chemotherapy is frequently used, but its activity is hampered by the development of drug resistance and many side effects. In this regard, the use of medicinal plants has been discussed, and in recent decades, the use of isolated phytochemicals came into the focus of interest. By critically evaluating the available evidence and emphasizing the unique perspective offered by this review, we provide insights into the potential of daidzein as a promising therapeutic agent, as well as outline future research directions to optimize its efficacy in clinical settings. To summarized the therapeutic potential of daidzein, an isoflavone phytoestrogen in the management of several human diseases with the focuses on the current status and future prospects as a therapeutic agent. Several search engines, including PubMed, GoogleScholar, and ScienceDirect, were used, with the search terms "daidzein", "daidzein therapeutic potential", or individual effects. The study included all peer-reviewed articles. However, the most recent publications were given priority. Daidzein showed protective effects against malignant diseases such as breast cancer, prostate cancer but also non-malignant diseases such as diabetes, osteoporosis, and cardiovascular diseases. Daidzein activates multiple signaling pathways leading to cell cycle arrest and apoptosis as well as antioxidant and anti-metastatic effects in malignant cells. Moreover, the anticancer effects against different cancer cells were more prominent and discussed in detail. In short, daidzein represents a promising compound for drug development. The comprehensive potential anticancer activities of daidzein through various molecular mechanisms and its therapeutic/clinical status required further detail studies. [ABSTRACT FROM AUTHOR]

Being a transcription factor, NF-κB regulates gene expressions involving cell survival and proliferation, drug resistance, metastasis, and angiogenesis. The activation of NF-κB plays a central role in the development of inflammation and cancer. Thus, the down-regulation of NF-κB may be an exciting target in prevention and treatment of cancer. NF-κB could act as a tumor activator or tumor suppressant decided by the site of action (organ). Polyphenols are widely distributed in plant species, consumption of which have been documented to negatively regulate the NF-κB signaling pathway. They depress the phosphorylation of kinases, inhibit NF-κB translocate into the nucleus as well as interfere interactions between NF-κB and DNA. Through inhibition of NF-κB, polyphenols downregulate inflammatory cascade, induce apoptosis and decrease cell proliferation and metastasis. This review highlights the anticancer effects of polyphenols on the basis of NF-κB signaling pathway regulation. [ABSTRACT FROM AUTHOR]

Doxorubicin (DOX) is a well-known chemotherapeutic agent extensively applied in the field of cancer therapy. However, similar to other chemotherapeutic agents such as cisplatin, paclitaxel, docetaxel, etoposide and oxaliplatin, cancer cells are able to obtain chemoresistance that limits DOX efficacy. In respect to dose-dependent side effect of DOX, enhancing its dosage is not recommended for effective cancer chemotherapy. Therefore, different strategies have been considered for reversing DOX resistance and diminishing its side effects. Phytochemical are potential candidates in this case due to their great pharmacological activities. Curcumin is a potential antitumor phytochemical isolated from Curcuma longa with capacity of suppressing cancer metastasis and proliferation and affecting molecular pathways. Experiments have demonstrated the potential of curcumin for inhibiting chemoresistance by downregulating oncogene pathways such as MMP-2, TGF-β, EMT, PI3K/Akt, NF-κB and AP-1. Furthermore, coadministration of curcumin and DOX potentiates apoptosis induction in cancer cells. In light of this, nanoplatforms have been employed for codelivery of curcumin and DOX. This results in promoting the bioavailability and internalization of the aforementioned active compounds in cancer cells and, consequently, enhancing their antitumor activity. Noteworthy, curcumin has been applied for reducing adverse effects of DOX on normal cells and tissues via reducing inflammation, oxidative stress and apoptosis. The current review highlights the anticancer mechanism, side effects and codelivery of curcumin and DOX via nanovehicles. [ABSTRACT FROM AUTHOR]

Cancer is one of the most extreme medical conditions in both developing and developed countries around the world, causing millions of deaths each year. Chemotherapy and/or radiotherapy are key for treatment approaches, but both have numerous adverse health effects. Furthermore, the resistance of cancerous cells to anticancer medication leads to treatment failure. The rising burden of cancer overall requires novel efficacious treatment modalities. Natural medications offer feasible alternative options against malignancy in contrast to western medication. Furanocoumarins' defensive and restorative impacts have been observed in leukemia, glioma, breast, lung, renal, liver, colon, cervical, ovarian, and prostate malignancies. Experimental findings have shown that furanocoumarins activate multiple signaling pathways, leading to apoptosis, autophagy, antioxidant, antimetastatic, and cell cycle arrest in malignant cells. Additionally, furanocoumarins have been shown to have chemo preventive and chemotherapeutic synergistic potential when used in combination with other anticancer drugs. Here, we address different pathways which are activated by furanocoumarins and their therapeutic efficacy in various tumors. Ideally, this review will trigger interest in furanocoumarins and their potential efficacy and safety as a cancer lessening agents. [ABSTRACT FROM AUTHOR]

A marked decrease in human cancers, including breast cancer, bone cancer, and cervical cancer, has been linked to the consumption of vegetable and fruit, and the corresponding chemoprotective effect has been associated with the presence of several active molecules, such as kaempferol. Kaempferol is a major flavonoid aglycone found in many natural products, such as beans, bee pollen, broccoli, cabbage, capers, cauliflower, chia seeds, chives, cumin, moringa leaves, endive, fennel, and garlic. Kaempferol displays several pharmacological properties, among them antimicrobial, anti-inflammatory, antioxidant, antitumor, cardioprotective, neuroprotective, and antidiabetic activities, and is being applied in cancer chemotherapy. Specifically, kaempferol-rich food has been linked to a decrease in the risk of developing some types of cancers, including skin, liver, and colon. The mechanisms of action include apoptosis, cell cycle arrest at the G2/M phase, downregulation of epithelial-mesenchymal transition (EMT)-related markers, and phosphoinositide 3-kinase/protein kinase B signaling pathways. In this sense, this article reviews data from experimental studies that investigated the links between kaempferol and kaempferol-rich food intake and cancer prevention. Even though growing evidence supports the use of kaempferol for cancer prevention, further preclinical and clinical investigations using kaempferol or kaempferol-rich foods are of pivotal importance before any public health recommendation or formulation using kaempferol. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is worldwide commonly found malignancy in women and effective treatment is regarded as a huge clinical challenge even in the presence of several options. Extensive literature is available that demonstrating polyphenols, the richly introduce phytopharmaceuticals as anticancer agents. Among these polyphenols, resveratrol, silibinin, quercetin, genistein, curcumin reported to have an awesome potential against breast cancer. However, till now no comprehensive survey found about the anticarcinogenic properties of luteolin against breast cancer.Scope and Approach: This review targeted the available literature on luteolin in the treatment of breast cancer, effects in combination with other anticancer drugs with possible mechanisms.Key Findings and Conclusion: An outstanding therapeutic potential of luteolin in the treatment of breast cancer has been recorded not just as a chemopreventive and chemotherapeutic agent yet complemented by its synergistic effects with other anticancer therapies such as cyclophosphamide, doxorubicin, and NSAID such as celecoxib, and possible underlying mechanisms. Ideally, this review will open new dimensions for luteolin as an effective and safe therapeutic agent in diminishing breast cancer. [ABSTRACT FROM AUTHOR]

Lymphoma is a cancer affecting the lymphatic system that fights infections and diseases. In addition to surgery, radiotherapy, and chemotherapy, novel approaches have recently been investigated, such as phytostilbenes in treating lymphoma. Phytostilbenes are natural compounds present in various plants and have been shown to have different therapeutic effects, including anticancer properties. Resveratrol is a main phytostilbene with various derivates followed by pterostilbene and piceatannol. Studies have revealed that phytostilbenes can suppress the growth and proliferation of lymphoma cells by inducing apoptosis and inhibiting specific enzyme activity in cancer cell survival. The compounds also have antiinflammatory effects contributing to reducing lymphoma-associated inflammation. Additionally, phytostilbenes have been shown to increase the immune system's ability to fight cancer cells by activating immune cells (T-cells and natural killer cells). This review investigates the potential therapeutic effects of phytostilbenes, including resveratrol, pterostilbene, piceatannol, and pinosylvin, against lymphoma. [Display omitted] •.Lymphoma is a cancer affecting the lymphatic system. • Phytostilbenes have shown diverse effects including anticancer. • Phytostilbenes can suppress the growth and proliferation of lymphoma cells via different mechanisms, described. • Phytostilbenes strengthened the immune system's ability to tbht cancer cells, described. • This review suggested the significant role of phytostilbenes as a potential ttherapeutic modality against lymphoma. [ABSTRACT FROM AUTHOR]

Despite the existence of extensive clinical research and novel therapeutic treatments, cancer remains undefeated and the significant cause of death worldwide. Cancer is a disease in which growth of cells goes out of control, being also able to invade other parts of the body. Cellular division is strictly controlled by multiple checkpoints like G1/S and G2/M which, when dysregulated, lead to uncontrollable cell division. The current remedies which are being utilized to combat cancer are monoclonal antibodies, chemotherapy, cryoablation, and bone marrow transplant etc. and these have also been greatly disheartening because of their serious adverse effects like hypotension, neuropathy, necrosis, leukemia relapse and many more. Bioactive compounds derived from natural products have marked the history of the development of novel drug therapies against cancer among which ginsenosides have no peer as they target several signaling pathways, which when abnormally regulated, lead to cancer. Substantial research has reported that ginsenosides like Rb1, Rb2, Rb3, Rc, Rd, Rg3, Rh2 etc. can prevent and treat cancer by targeting different pathways and molecules by induction of autophagy, neutralizing ROS, induction of cancerous cell death by controlling the p53 pathway, modulation of miRNAs by decreasing Smad2 expression, regulating Bcl-2 expression by normalizing the NF-Kb pathway, inhibition of inflammatory pathways by decreasing the production of cytokines like IL-8, causing cell cycle arrest by restricting cyclin E1 and CDC2, and induction of apoptosis during malignancy by decreasing β-catenin levels etc. In this review, we have analyzed the anti-cancer therapeutic potential of various ginsenoside compounds in order to consider their possible use in new strategies in the fight against cancer. [Display omitted] • Use of ginsenosides as a possible a new strategy in fighting cancer. • Ginsenosides display anti-cancer activity through regulation of cell cycle and apoptosis. • New dimension of the antitumor effects of ginsenosides in various cancers. [ABSTRACT FROM AUTHOR]

Malignant melanoma is the most dangerous type of skin cancer. It is becoming more common globally and is increasingly resistant to treatment options. Despite extensive research into its pathophysiology, there are still no proven cures for metastatic melanoma. Unfortunately, current treatments are frequently ineffective and costly, and have several adverse effects. Natural substances have been extensively researched for their anti-MM capabilities. Chemoprevention and adjuvant therapy with natural products is an emerging strategy to prevent, cure or treat melanoma. Numerous prospective drugs are found in aquatic species, providing a plentiful supply of lead cytotoxic chemicals for cancer treatment. Anticancer peptides are less harmful to healthy cells and cure cancer through several different methods, such as altered cell viability, apoptosis, angiogenesis/metastasis suppression, microtubule balance disturbances and targeting lipid composition of the cancer cell membrane. This review addresses marine peptides as effective and safe treatments for MM and details their molecular mechanisms of action. [ABSTRACT FROM AUTHOR]

Abnormalities in the mitogen-activated protein kinase (MAPK) signaling pathway are a key contributor to the carcinogenesis process and have therefore been implicated in several aspects of tumorigenesis, including cell differentiation, proliferation, invasion, angiogenesis, apoptosis, and metastasis. This pathway offers multiple molecular targets that may be modulated for anticancer activity and is of great interest for several malignancies. Polyphenols from various dietary sources have been observed to interfere with certain aspects of this pathway and consequently play a substantial role in the development and progression of cancer by suppressing cell growth, inactivating carcinogens, blocking angiogenesis, causing cell death, and changing immunity. A good number of polyphenolic compounds have shown promising outcomes in numerous pieces of research and are currently being investigated clinically to treat cancer patients. The current study concentrates on the role of the MAPK pathway in the development and metastasis of cancer, with particular emphasis on dietary polyphenolic compounds that influence the different MAPK sub-pathways to obtain an anticancer effect. This study aims to convey an overview of the various aspects of the MAPK pathway in cancer development and invasion, as well as a review of the advances achieved in the development of polyphenols to modulate the MAPK signaling pathway for better treatment of cancer. [Display omitted] [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor in humans. It is characterized by excessive cell growth and accelerated intrusion of normal brain tissue along with a poor prognosis. The current standard of treatment, including surgical removal, radiation therapy, and chemotherapy, is largely ineffective, with high mortality and recurrence rates. As a result, traditional approaches have evolved to include new alternative remedies, such as natural compounds. Aquatic species provide a rich supply of possible drugs. The physiological effects of marine peptides in glioblastoma are mediated by a range of pathways, including apoptosis, microtubule balance disturbances, suppression of angiogenesis, cell migration/invasion, and cell viability; autophagy and metabolic enzymes downregulation. Herein, we address the efficacy of marine peptides as putative safe therapeutic agents for glioblastoma coupled with detail molecular mechanisms. • Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor in humans. • The current treatment for GBM is largely ineffective, with high mortality and recurrence rates. • Traditional approaches including aquatic species have provide a rich supply of possible drugs. • The physiological effects of marine peptides in GBM are mediated by modulation of multiple pathways. • Marine peptides are found as putative safe therapeutic agents for the treatment of glioblastoma. [ABSTRACT FROM AUTHOR]

Cancer is the second leading cause of death worldwide. Majority of recent research efforts in the field aim to address why cancer resistance to therapy develops and how to overcome or prevent it. In line with this, novel anti-cancer compounds are desperately needed for chemoresistant cancer cells. Phytochemicals, in view of their pharmacological activities and capacity to target various molecular pathways, are of great interest in the development of therapeutics against cancer. Plant-derived-natural products have poor bioavailability which restricts their anti-tumor activity. Gallic acid (GA) is a phenolic acid exclusively found in natural sources such as gallnut, sumac, tea leaves, and oak bark. In this review, we report on the most recent research related to anti-tumor activities of GA in various cancers with a focus on its underlying molecular mechanisms and cellular pathwaysthat that lead to apoptosis and migration of cancer cells. GA down-regulates the expression of molecular pathways involved in cancer progression such as PI3K/Akt. The co-administration of GA with chemotherapeutic agents shows improvements in suppressing cancer malignancy. Various nano-vehicles such as organic- and inorganic nano-materials have been developed for targeted delivery of GA at the tumor site. Here, we suggest that nano-vehicles improve GA bioavailability and its ability for tumor suppression. [Display omitted] • Gallic acid (GA) is a naturally occurring phenolic acid compound. • GA stimulates apoptosis in tumor cells and suppresses their migration. • GA enhances sensitivity of tumor cells to chemotherapy. • Molecular pathways such as PI3K/Akt, ERK and NF-κB are affected by GA. • Nanostructures improve bioavailability and intracellular accumulation of GA. [ABSTRACT FROM AUTHOR]

Breast cancer is the most prevalent invasive form of cancer in females and posing a great challenge for overcoming disease burden. The growth in global cancer deaths mandates the discovery of new efficacious natural anti-tumor treatments. In this regard, aquatic species offer a rich supply of possible drugs. Studies have shown that several marine peptides damage cancer cells by a broad range of pathways, including apoptosis, microtubule balance disturbances, and suppression of angiogenesis. Traditional chemotherapeutic agents are characterized by a plethora of side effects, including immune response suppression. The discovery of novel putative anti-cancer peptides with lesser toxicity is therefore necessary and timely, especially those able to thwart multi drug resistance (MDR). This review addresses marine anti-cancer peptides for the treatment of breast cancer. • Breast cancer is the most prevalent invasive form of cancer in females. • The troubling rise in global cancer deaths mandates search for new natural anti-tumor medicines. • Marine peptides damage cancer cells by apoptosis, microtubule balance disturbances, and suppression of angiogenesis. • Marine anti-cancer peptides appear less toxic to normal cells than traditional treatments. • Marine peptides are capable of blocking MDR affording an efficient treatment modality. [ABSTRACT FROM AUTHOR]

As a phenolic acid compound, caffeic acid (CA) can be isolated from different sources such as tea, wine and coffee. Caffeic acid phenethyl ester (CAPE) is naturally occurring derivative of CA isolated from propolis. This medicinal plant is well-known due to its significant therapeutic impact including its effectiveness as hepatoprotective, neuroprotective and anti-diabetic agent. Among them, anti-tumor activity of CA has attracted much attention, and this potential has been confirmed both in vitro and in vivo. CA can induce apoptosis in cancer cells via enhancing ROS levels and impairing mitochondrial function. Molecular pathways such as PI3K/Akt and AMPK with role in cancer progression, are affected by CA and its derivatives in cancer therapy. CA is advantageous in reducing aggressive behavior of tumors via suppressing metastasis by inhibiting epithelial-to-mesenchymal transition mechanism. Noteworthy, CA and CAPE can promote response of cancer cells to chemotherapy, and sensitize them to chemotherapy-mediated cell death. In order to improve capacity of CA and CAPE in cancer suppression, it has been co-administered with other anti-tumor compounds such as gallic acid and p-coumaric acid. Due to its poor bioavailability, nanocarriers have been developed for enhancing its ability in cancer suppression. These issues have been discussed in the present review with a focus on molecular pathways to pave the way for rapid translation of CA for clinical use. [Display omitted] • Caffeic acid (CA) is a member of phenolic acid family of polyphenols. • CA and its derivatives can induce both apoptosis and autophagy in cancer cells. • CA and its derivatives impair migration and metastasis of cancer cells. • CA and its derivatives promote radio- and chemo-sensitivity of cancer cells. • Nanoparticles promote therapeutic effect of CA and CAPE in reducing cancer cell malignancy. [ABSTRACT FROM AUTHOR]

Lung cancer (LC) is a leading cause of death worldwide with high mortality and morbidity. A wide variety of risk factors are considered for LC development such as smoking, air pollution and family history. It appears that genetic and epigenetic factors are also potential players in LC development and progression. AMP-activated protein kinase (AMPK) is a signaling pathway with vital function in inducing energy balance and homeostasis. An increase in AMP:ATP and ADP:ATP ratio leads to activation of AMPK signaling by upstream mediators such as LKB1 and CamKK. Dysregulation of AMPK signaling is a common finding in different cancers, particularly LC. AMPK activation can significantly enhance LC metastasis via EMT induction. Upstream mediators such as PLAG1, IMPAD1, and TUFM can regulate AMPK-mediated metastasis. AMPK activation can promote proliferation and survival of LC cells via glycolysis induction. In suppressing LC progression, anti-tumor compounds including metformin, ginsenosides, casticin and duloxetine dually induce/inhibit AMPK signaling. This is due to double-edged sword role of AMPK signaling in LC cells. Furthermore, AMPK signaling can regulate response of LC cells to chemotherapy and radiotherapy that are discussed in the current review. [Display omitted] [ABSTRACT FROM AUTHOR]

The complex pathophysiological mechanisms behind destructive chronic conditions, including cancer, neurodegenerative diseases, diabetes mellitus, cardiovascular diseases, and hepatic failure urge the need for finding related pivotal dysregulated signaling mediators, as well as multi-target therapeutic agents. In the current study, critical roles of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway, as potential therapeutic targets in the pathogenesis of various diseases has been described. This pathway is also interconnected with several downstream inflammatory, oxidative stress, and apoptotic mediators, as dysregulated pathways in chronic diseases. Therefore, identifying novel multi-target agents to attenuate PI3K/Akt, thereby related downstream pathways, is of great importance. Astaxanthin (AST) is a multi-target lipid-soluble keto-carotenoid derived from the varieties of marine organisms, with potential anti-inflammatory, antioxidant and antiapoptotic properties through PI3K/Akt pathway. Nowadays, due to its high nutritional and medicinal value, research on AST is increasing. This review aimed to address PI3K/Akt targeted by AST in several diseases toward clinical applications. Image 1 • The PI3K/Akt pathway plays a critical role in the pathogenesis of different diseases. • The PI3K/Akt pathway has a close interconnection with other inflammatory, apoptotic and oxidative stress pathways. • Astaxanthin passes through PI3K/Akt pathway toward potential therapeutic application. • Astaxanthin could attenuate mTOR, GSK-3β, HIF-1α, Bcl-2, Bad, FoxO and other interconnected mediators through PI3K/Akt. • Astaxanthin is a potential carotenoid with auspicious biological activities and health benefits. [ABSTRACT FROM AUTHOR]

Cancer cells underlie the dysregulated metabolism of carbohydrate, lipid and protein and thereby, employ interconnected cross-linked signaling pathways to supply adequate energy for growth and related biosynthetic procedures. In the present study, a comprehensive review of cancer metabolism and anthocyanin's effect was conducted using the existing electronic databases, including Medline, PubMed, Scopus, and Web of Science, as well as related articles in the field. Such keywords as "cancer", and "cancer metabolism" in the title/abstract/keyword and all the "anthocyanins" in the whole text were used. Data were collected without time restriction until February 2020. The results indicated the involvement of several signaling pathways, including inflammatory PI3K/Akt/mTOR pathway, Bax/Bcl-2/caspases as apoptosis modulators, and NF-κB/Nrf2 as oxidative stress mediators in the cancer dysregulated metabolism. Compelling studies have shown that targeting these pathways, as critical hallmarks of cancer, plays a critical role in combating cancer dysregulated metabolism. The complexity of cancer metabolism signaling pathways, along with toxicity, high costs, and resistance to conventional drugs urge the need to investigate novel multi-target agents. Increasing evidence has introduced plant-derived secondary metabolites as hopeful anticancer candidates which target multiple dysregulated cross-linked pathways of cancer metabolism. Amongst these metabolites, anthocyanins have demonstrated positive anticancer effects by targeting inflammation, oxidative stress, and apoptotic signaling pathways. The current study revealed the cross-linked signaling pathways of cancer metabolism, as well as the promising pharmacological mechanisms of anthocyanins in targeting the aforementioned signaling mediators. To overcome the pharmacokinetic limitations of anthocyanins in cancer treatment, their interactions with gut microbiota and the need to develop related nano-formulations were also considered. [ABSTRACT FROM AUTHOR]