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Chemotherapeutics are most often used to treat cancer, but side effects, drug resistance, and toxicity often compromise their effectiveness. In contrast, phytocompound plumbagin possesses a distinct pleiotropic nature, targeting multiple signaling pathways, such as ROS generation, cell death, cellular proliferation, metastasis, and drug resistance, and is shown to enhance the efficacy of chemotherapeutic drugs. Plumbagin has been shown to act synergistically with various chemotherapeutic drugs and enhance their efficacy in drug-resistant cancers. The pleiotropic nature is believed to be due to plumbagin's unique structure, which contains a naphthoquinone ring and a hydroxyl group responsible for plumbagin's various biological responses. Despite limitations such as restricted bioavailability and delivery, recent developments aim to address these challenges and harness the potential of plumbagin as an anticancer therapeutics. This review delves into the structural aspect of the plumbagin molecule contributing to its pleiotropic nature, explores the diverse mechanism that it targets, and discusses emerging strategies to overcome its limitations., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Radiotherapy is a cornerstone in the treatment of solid tumors, with extensive Phase III trials confirming its effectiveness. As advancements in treatment technologies and our understanding of tumor resistance mechanisms continue, the role of radiation oncology is set to become even more pivotal. Addressing the global challenge of lethal cancers demands innovative strategies, particularly in minimizing the side effects associated with traditional chemotherapy and ionizing radiation (IR). Recently, there has been growing interest in natural compounds for radioprotection, aiming to prevent tumor development and metastasis. Piperine, a compound found in black and long pepper, has emerged as a promising chemopreventive agent that works effectively without harming normal cells. Mechanistically, piperine modulates key signaling pathways, inhibits cancer cell migration and invasion, and enhances sensitivity to IR. Combining piperine with radiotherapy offers a compelling approach, boosting treatment efficacy while protecting healthy tissues from radiation damage. Piperine's versatile role goes beyond radiosensitization to include radioprotection by inhibiting NF-κB activation, reducing autophagy, and promoting apoptosis in cancer cells. This dual action makes it a promising candidate for personalized cancer care. As research advances, the therapeutic potential of piperine may drive new frontiers in cancer treatment strategies., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Phytochemicals possess a wide range of anti-tumor properties, including the modulation of autophagy and regulation of programmed cell death. Autophagy is a critical process in cellular homeostasis and its dysregulation is associated with several pathological conditions, such as cancer, neurodegenerative diseases, and diabetes. In cancer, autophagy plays a dual role by either promoting tumor growth or suppressing it, depending on the cellular context. During autophagy, autophagosomes engulf cytoplasmic components such as proteins and organelles. LC3-II (microtubule-associated protein 1 light chain 3-II) is an established marker of autophagosome formation, making it central to autophagy monitoring in mammals., Objective: To explore the regulatory role of phytochemicals in LC3-mediated autophagy and their potential therapeutic impact on cancer. The review emphasizes the involvement of autophagy in tumor promotion and suppression, particularly focusing on autophagy-related signaling pathways like oxidative stress through the NRF2 pathway, and its implications for genomic stability in cancer development., Methods: The review focuses on a comprehensive analysis of bioactive compounds including Curcumin, Celastrol, Resveratrol, Kaempferol, Naringenin, Carvacrol, Farnesol, and Piperine. Literature on these compounds was examined to assess their influence on autophagy, LC3 expression, and tumor-related signaling pathways. A systematic literature search was conducted across databases including PubMed, Scopus, and Web of Science from inception to 2023. Studies were selected from prominent databases, focusing on their roles in cancer diagnosis and therapeutic interventions, particularly in relation to LC3-mediated mechanisms., Results: Phytochemicals have been shown to modulate autophagy through the regulation of LC3-II levels and autophagic flux in cancer cells. The interaction between autophagy and other cellular pathways such as oxidative stress, inflammation, and epigenetic modulation highlights the complex role of autophagy in tumor biology. For instance, Curcumin and Resveratrol have been reported to either induce or inhibit autophagy depending on cancer type, influencing tumor progression and therapeutic responses., Conclusion: Targeting autophagy through LC3 modulation presents a promising strategy for cancer therapy. The dual role of autophagy in tumor suppression and promotion, however, necessitates careful consideration of the context in which autophagy is induced or inhibited. Future research should aim to delineate these context-specific roles and explore how phytochemicals can be optimized for therapeutic efficacy. Novel therapeutic strategies should focus on the use of bioactive compounds to fine-tune autophagy, thereby maximizing tumor suppression and inducing programmed cell death in cancer cells., (© 2024 The Author(s). Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

In this comprehensive review we tried to reassess the role of phytochemicals in cancer chemoprevention. The exploration of the "synergistic effect" concept, advocating combined chemopreventive agents, faces challenges like low bioavailability. The review incorporates personal, occasionally controversial, viewpoints on natural compounds' cancer preventive capabilities, delving into mechanisms. Prioritizing significant contributions within the vast research domain, we aim stimulating discussion to provide a comprehensive insight into the evolving role of phytochemicals in cancer prevention. While early years downplayed the role of phytochemicals, the late nineties witnessed a shift, with leaders exploring their potential alongside synthetic compounds. Challenges faced by chemoprevention, such as limited pharmaceutical interest and cost-effectiveness issues, persist despite successful drugs. Recent studies, including the EPIC study, provide nuanced insights, indicating a modest risk reduction for increased fruit and vegetable intake. Phytochemicals, once attributed to antioxidant effects, face scrutiny due to low bioavailability and conflicting evidence. The Nrf2-EpRE signaling pathway and microbiota-mediated metabolism emerge as potential mechanisms, highlighting the complexity of understanding phytochemical mechanisms in cancer chemoprevention., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Due to the complex pathophysiological mechanisms involved in cancer progression and metastasis, current therapeutic approaches lack efficacy and have significant adverse effects. Therefore, it is essential to establish novel strategies for combating cancer. Phytochemicals, which possess multiple biological activities, such as antioxidant, anti-inflammatory, antimutagenic, immunomodulatory, antiproliferative, anti-angiogenesis, and antimetastatic properties, can regulate cancer progression and interfere in various stages of cancer development by suppressing various signaling pathways., Methods: The current systematic and comprehensive review was conducted based on Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) criteria, using electronic databases, including PubMed, Scopus, and Science Direct, until the end of December 2023. After excluding unrelated articles, 111 related articles were included in this systematic review., Results: In this current review, the major signaling pathways of cancer metabolism are highlighted with the promising anticancer role of phytochemicals. This was through their ability to regulate the AMP-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) signaling pathway. The AMPK/PGC-1α signaling pathway plays a crucial role in cancer cell metabolism via targeting energy homeostasis and mitochondria biogenesis, glucose oxidation, and fatty acid oxidation, thereby generating ATP for cell growth. As a result, targeting this signaling pathway may represent a novel approach to cancer treatment. Accordingly, alkaloids, phenolic compounds, terpene/terpenoids, and miscellaneous phytochemicals have been introduced as promising anticancer agents by regulating the AMPK/PGC-1α signaling pathway. Novel delivery systems of phytochemicals targeting the AMPK/PGC-1α pathway in combating cancer are also highlighted in this review., (© 2024. The Author(s).)

Abstract: Cancer development takes 10 to 50 years, and epigenetics plays an important role. Recent evidence suggests that ~80% of human cancers are linked to environmental factors impinging upon genetics/epigenetics. Because advanced metastasized cancers are resistant to radiation/chemotherapeutic drugs, cancer prevention by relatively nontoxic "epigenetic modifiers" will be logical. Many dietary phytochemicals possess powerful antioxidant and anti-inflammatory properties that are hallmarks of cancer prevention. Dietary phytochemicals can regulate gene expression of the cellular genome via epigenetic mechanisms. In this review, we will summarize preclinical studies that demonstrate epigenetic mechanisms of dietary phytochemicals in skin, colorectal, and prostate cancer prevention. Key examples of the importance of epigenetic regulation in carcinogenesis include hypermethylation of the NRF2 promoter region in cancer cells, resulting in inhibition of NRF2-ARE signaling. Many dietary phytochemicals demethylate NRF2 promoter region and restore NRF2 signaling. Phytochemicals can also inhibit inflammatory responses via hypermethylation of inflammation-relevant genes to block gene expression. Altogether, dietary phytochemicals are excellent candidates for cancer prevention due to their low toxicity, potent antioxidant and anti-inflammatory properties, and powerful epigenetic effects in reversing procarcinogenic events., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. This work was supported in part by institutional funds and by R01 AT009152 from the National Center for Complementary and Integrative Health, R01 CA200129 from the National Cancer Institute, and P30 ES005022 from the National Institute of Environmental Health., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The main active constituents of plants of the Paeonia genus are known to have antitumor activity. Hundreds of compounds with a wide range of pharmacological activities, including monoterpene glycosides, flavonoids, tannins, stilbenes, triterpenoids, steroids, and phenolic compounds have been isolated. Among them, monoterpenes and their glycosides, flavonoids, phenolic acids, and other constituents have been shown to have good therapeutic effects on various cancers, with the main mechanisms including the induction of apoptosis; the inhibition of tumor cell proliferation, migration, and invasion; and the modulation of immunity. In this study, many citations related to the traditional uses, phytochemical constituents, antitumor effects, and clinical applications of the Paeonia genus were retrieved from popular and widely used databases such as Web of Science, Science Direct, Google Scholar, and PubMed using different search strings. A systematic review of the antitumor constituents of the Paeonia genus and their therapeutic effects on various cancers was conducted and the mechanisms of action and pathways of these phytochemicals were summarised to provide a further basis for antitumor research., (© 2024. The Pharmaceutical Society of Korea.)

Autophagy and endoplasmic reticulum (ER) stress are conserved processes that generally promote survival, but can induce cell death when physiological thresholds are crossed. The pro-survival aspects of these processes are exploited by cancer cells for tumor development and progression. Therefore, anticancer drugs targeting autophagy or ER stress to induce cell death and/or block the pro-survival aspects are being investigated extensively. Consistently, several phytochemicals have been reported to exert their anticancer effects by modulating autophagy and/or ER stress. Various phytochemicals (e.g., celastrol, curcumin, emodin, resveratrol, among others) activate the unfolded protein response to induce ER stress-mediated apoptosis through different pathways. Similarly, various phytochemicals induce autophagy through different mechanisms (namely mechanistic target of Rapamycin [mTOR] inhibition). However, phytochemical-induced autophagy can function either as a cytoprotective mechanism or as programmed cell death type II. Interestingly, at times, the same phytochemical (e.g., 6-gingerol, emodin, shikonin, among others) can induce cytoprotective autophagy or programmed cell death type II depending on cellular contexts, such as cancer type. Although there is well-documented mechanistic interplay between autophagy and ER stress, only a one-way modulation was noted with some phytochemicals (carnosol, capsaicin, cryptotanshinone, guangsangon E, kaempferol, and δ-tocotrienol): ER stress-dependent autophagy. Plant extracts are sources of potent phytochemicals and while numerous phytochemicals have been investigated in preclinical and clinical studies, the search for novel phytochemicals with anticancer effects is ongoing from plant extracts used in traditional medicine (e.g., Origanum majorana). Nonetheless, the clinical translation of phytochemicals, a promising avenue for cancer therapeutics, is hindered by several limitations that need to be addressed in future studies., (© 2024 The Author(s). Phytotherapy Research published by John Wiley & Sons Ltd.)

Background: Cancer is the most common cause of death and is still a serious public health problem. Alkaloids, a class of bioactive compounds widely diffused in plants, especially Chinese herbs, are used as functional ingredients, precursors, and lead compounds in food and clinical applications. Among them, aporphine alkaloids (AAs), as an important class of isoquinoline alkaloids, exert a strong anticancer effect on multiple cancer types., Aim of Review: This review aims to comprehensively summarize the phytochemistry, pharmacokinetics, and bioavailability of seven subtypes of AAs and their derivatives from various plants and highlight their anticancer bioactivities and mechanisms of action. Key Scientific Concepts of Review. The chemical structures and botanical diversity of AAs are elucidated, and promising results are highlighted regarding the potent anticancer activities of AAs and their derivatives, contributing to their pharmacological benefits. This work provides a better understanding of AAs and combinational anticancer therapies involving them, thereby improving the development of functional food containing plant-derived AA and the clinical application of AAs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Production and hosting by Elsevier B.V.)

According to worldwide health data, cancer, and inflammatory illnesses are on the rise and are among the most common causes of death. Across the world, these types of health problems are now considered top priorities for government health organizations. Hence, this study aimed to investigate medicinal plants' potential for treating cancer and inflammatory disorders. This network pharmacology analysis aims to learn more about the potential targets and mechanisms of action for the bioactive ingredients in Sauropus androgynus (L.) Merr L. The compound-target network and protein-protein interaction analysis were built using the STRING database. Using Network Analyst, Gene Ontology, and Kyoto Encyclopaedia of Genes and Genomes, pathway enrichment was performed on the hub genes. 1-hexadecanol was shown to inhibit drug-metabolizing enzymes in a pharmacokinetic investigation. Those samples of 1-hexadecanol were found to be 1-hexadecanol (BBB 0.783), GI High, Pgp Substrate Yes, CYP2C19 Inhibitor Yes, CYP2D6 Yes, and HI -89.803. The intermolecular binding energies for 1-hexadecanol (4-DRI, -8.2 kcal/mol) are evaluated. These results from a study on S. androgynus used molecular docking and network pharmacology to gain insight into the prime target genes and potential mechanisms identified for AKT1, mTOR, AR, PPID, FKBP5, and NR3C1. The PI3K-Akt signalling pathway has become an important regulatory node in various pathological processes requiring coordinated actions. Stability and favourable conformations have been resolved by considering nonbonding interactions such as electrostatic and hydrogen bonds in MD simulations of the perfect molecules using the Desmond package. Thus, using an appropriate platform of network pharmacology, molecular docking, and in vitro experiments, this study provides for the first time a clearer knowledge of the anti-cancer and anti-inflammatory molecular bioactivities of S. androgynus. Further in vitro and in vivo confirmations are strongly needed to determine the efficacy and therapeutic effects of 1-hexadecanol in the biological process.Communicated by Ramaswamy H. Sarma.

With the increasing global incidence and mortality rates of cancer, the development of novel anti-tumor drugs has become particularly urgent. Scutellaria barbata D. Don, a perennial herb belonging to the genus Scutellaria in the family Lamiaceae, has aroused extensive attention for its medicinal value in recent years. This article presents an exhaustive review of the flavonoid, diterpene, and other chemical constituents harbored within Scutellaria barbata , delving into the intricate mechanisms by which these compounds orchestrate their anti-tumor effects via diverse biological pathways. Remarkably, these compounds distinguish themselves through their capability to regulate cellular signaling, inhibit cancer cell proliferation, trigger apoptosis, disrupt angiogenesis, and bolster immune responses. These anti-tumor effects are achieved through strategic modulation of pivotal signaling cascades, particularly the PI3K/Akt/mTOR, MAPK, and NFκB pathways. In addition, this article also summarizes the clinical applications of Scutellaria barbata in tumor treatment, especially its potential in alleviating the side effects of radiotherapy and chemotherapy and improving patients' quality of life. In conclusion, this review comprehensively summarizes and analyzes the chemical constituents, anti-tumor mechanisms, and clinical applications of Scutellaria barbata , with the aim of systematically reviewing the existing research results and exploring potential future research directions.

Cancer is a complex disease that affects millions of people and remains a major public health problem worldwide. Conventional cancer treatments, including surgery, chemotherapy, immunotherapy, and radiotherapy, have limited achievements and multiple drawbacks, among which are healthy tissue damage and multidrug-resistant phenotype onset. Increasing evidence shows that many plants' natural products, as well as their bioactive compounds, have promising anticancer activity and exhibit minimal toxicity compared to conventional anticancer drugs. However, their widespread use in cancer therapy is severely restricted by limitations in terms of their water solubility, absorption, lack of stability, bioavailability, and selective targeting. The use of nanoformulations for plants' natural product transportation and delivery could be helpful in overcoming these limitations, thus enhancing their therapeutic efficacy and providing the basis for improved anticancer treatment strategies. The present review is aimed at providing an update on some phytocompounds (curcumin, resveratrol, quercetin, and cannabinoids, among others) and their main nanoformulations showing antitumor activities, both in vitro and in vivo, against such different human cancer types as breast and colorectal cancer, lymphomas, malignant melanoma, glioblastoma multiforme, and osteosarcoma. The intracellular pathways underlying phytocompound anticancer activity and the main advantages of nanoformulation employment are also examined. Finally, this review critically analyzes the research gaps and limitations causing the limited success of phytocompounds' and nanoformulations' clinical translation.

Significance: Peroxisome proliferator-activated receptors (PPARs) have a moderately preserved amino-terminal domain, an extremely preserved DNA-binding domain, an integral hinge region, and a distinct ligand-binding domain that are frequently encountered with the other nuclear receptors. PPAR-β/δ is among the three nuclear receptor superfamily members in the PPAR group. Recent Advances: Emerging studies provide an insight on natural compounds that have gained increasing attention as potential anticancer agents due to their ability to target multiple pathways involved in cancer development and progression. Critical Issues: Modulation of PPAR-β/δ activity has been suggested as a potential therapeutic strategy for cancer management. This review focuses on the ability of bioactive phytocompounds to impact reactive oxygen species (ROS) and redox signaling by targeting PPAR-β/δ for cancer therapy. The rise of ROS in cancer cells may play an important part in the initiation and progression of cancer. However, excessive levels of ROS stress can also be toxic to the cells and cancer cells with increased oxidative stress are likely to be more vulnerable to damage by further ROS insults induced by exogenous agents, such as phytocompounds and therapeutic agents. Therefore, redox modulation is a way to selectively kill cancer cells without causing significant toxicity to normal cells. However, use of antioxidants together with cancer drugs may risk the effect of treatment as both act through opposite mechanisms. Future Directions: It is advisable to employ more thorough and detailed methodologies to undertake mechanistic explorations of numerous phytocompounds. Moreover, conducting additional clinical studies is recommended to establish optimal dosages, efficacy, and the impact of different phytochemicals on PPAR-β/δ.

Cancer is a complicated and ever-evolving disease that remains a significant global cause of disease and mortality. Its complexity, which is evident at the genetic and phenotypic levels, contributes to its diversity and resistance to treatment. Numerous scientific investigations on human and animal models demonstrate the potential of phytochemicals in cancer prevention. Coffee has been shown to possess potent anti-carcinogenic properties, and studies have documented the consumption of coffee as a beverage reduces the risk of cancer occurrence. The major secondary metabolites of coffee, named caffeine and chlorogenic acid, have been linked to anti-inflammatory and antineoplastic effects through various signaling. In light of this, this review article provides a comprehensive analysis based on studies in anticancer effects of coffee, chlorogenic acid, and caffeine published between 2010 and 2023, sourced from Scopus, Pubmed, and Google Scholar databases. We summarize recent advances and scientific evidence on the association of phytochemicals found in coffee with a special emphasis on their biological activities against cancer and their molecular mechanism deemed potential to be used as a novel therapeutic target for cancer prevention and therapy.

This comprehensive review delves into the multifaceted aspects of genipin, a bioactive compound derived from medicinal plants, focusing on its anti-cancer potential. The review begins by detailing the sources and phytochemical properties of genipin, underscoring its significance in traditional medicine and its transition into contemporary cancer research. It then explores the intricate relationship between genipin's chemical structure and its observed anti-cancer activity, highlighting the molecular underpinnings contributing to its therapeutic potential. This is complemented by a thorough analysis of preclinical studies, which investigates genipin's efficacy against various cancer cell lines and its mechanisms of action at the cellular level. A crucial component of the review is the examination of genipin's bioavailability and pharmacokinetics, providing insights into how the compound is absorbed, distributed, metabolized, and excreted in the body. Then, this review offers a general and updated overview of the anti-cancer studies of genipin and its derivatives based on its basic molecular mechanisms, induction of apoptosis, inhibition of cell proliferation, and disruption of cancer cell signaling pathways. We include information that complements the genipin study, such as toxicity data, and we differentiate this review by including commercial status, disposition, and regulation. Also, this review of genipin stands out for incorporating information on proposals for a technological approach through its load in nanotechnology to improve its bioavailability. The culmination of this information positions genipin as a promising candidate for developing novel anti-cancer drugs capable of supplementing or enhancing current cancer therapies., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This Special Issue focused on the importance of phytochemicals for their use in the prevention and treatment of cancer [...].

Ethnopharmacological Relevance: Infection and inflammation are critical to global human health status and the goal of current pharmacological interventions intends formulating medications/preventives as a measure to deal with this situation. Chemokines and their cognate receptors are major regulatory molecules in many of these ailments. Natural products have been a keen source to the drug development industry, every year contributing significantly to the growing list of FDA approved drugs. A multiverse of natural resource is employed as a part of curative regimen in folk/traditional/ethnomedicine which can be employed to discover, repurpose, and design potent medications for the diseases of clinical concern., Aim of the Study: This review aims to systematically document the ethnopharmacologically active agents targeting the infectious-inflammatory diseases through the chemokine-receptor nexus., Materials and Methods: Articles related to chemokine/receptor modulating ethnopharmacological anti-inflammatory, anti-infectious natural sources, bioactive compounds, and formulations have been examined with special emphasis on women related diseases. The available literature has been thoroughly scrutinized for the application of traditional medicines in chemokine associated experimental methods, their regulatory outcomes, and pertinence to women's health wherever applicable. Moreover, the potential traditional regimens under clinical trials have been critically assessed., Results: A systematic and comprehensive review on the chemokine-receptor targeting ethnopharmaceutics from the available literature has been provided. The article discusses the implication of traditional medicine in the chemokine system dynamics in diverse infectious-inflammatory disorders such as cardiovascular diseases, allergic diseases, inflammatory diseases, neuroinflammation, and cancer. On this note, critical evaluation of the available data surfaced multiple diseases prevalent in women such as osteoporosis, rheumatoid arthritis, breast cancer, cervical cancer and urinary tract infection. Currently there is no available literature highlighting chemokine-receptor targeting using traditional medicinal approach from women's health perspective. Moreover, despite being potent in vitro and in vivo setups there remains a gap in clinical translation of these formulations, which needs to be strategically and scientifically addressed to pave the way for their successful industrial translation., Conclusions: The review provides an optimistic global perspective towards the applicability of ethnopharmacology in chemokine-receptor regulated infectious and inflammatory diseases with special emphasis on ailments prevalent in women, consecutively addressing their current status of clinical translation and future directions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The study of chemicals extracted from natural sources should be encouraged due to the significant number of cancer deaths each year and the financial burden imposed by this disease on society. The causes of almost all cancers involve a combination of lifestyle, environmental factors, and genetic and inherited factors. Modern medicine researchers are increasingly interested in traditional phytochemicals as they hold potential for new bioactive compounds with medical applications. Recent publications have provided evidence of the antitumor properties of phytochemicals, a key component of traditional Chinese medicine, thereby opening new avenues for their use in modern medicine. Various studies have demonstrated a strong correlation between apoptosis and autophagy, two critical mechanisms involved in cancer formation and regulation, indicating diverse forms of crosstalk between them. Phytochemicals have the ability to activate both pro-apoptotic and pro-autophagic pathways. Therefore, understanding how phytochemicals influence the relationship between apoptosis and autophagy is crucial for developing a new cancer treatment strategy that targets these molecular mechanisms. This review aims to explore natural phytochemicals that have demonstrated anticancer effects, focusing on their role in regulating the crosstalk between apoptosis and autophagy, which contributes to uncontrolled tumor cell growth. Additionally, the review highlights the limitations and challenges of current research methodologies while suggesting potential avenues for future research in this field., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest, (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Ethnopharmacological Relevance: Cancer stands as one of the leading causes of death worldwide according to the World Health Organization (WHO), and it has led to approximately 10 million fatalities in 2020. Medicinal plants are still widely used and accepted form of treatment for most diseases including cancer in Ghana. This review presented Cryptolepis nigrescens (Wennberg) L. Joubert. and Bruyns., Prosopsis africana (Guill. and Perr.) Taub. and Pterygota macrocarpa K. Schum. as medicinal plants that are traditionally used to treat tumour growth, amongst other diseases, in the Ashanti region of Ghana., Aim of Review: This paper aims to present a comprehensive review on the botanical description, ecological distribution, ethnomedicinal uses, phytochemical composition and ethnopharmacological relevance of C. nigrescens, P. africana and P. macrocarpa., Materials and Methods: The review covers works published between 1962 and 2023 from various countries. Published books, thesis, scientific and medical articles on C. nigrescens, P. africana and P. macrocarpa were collected from the following databases: 'Scopus', 'Science Direct', 'Medline', 'PubMed', 'Research Gate' 'Google Scholar, and 'Springer link' using the keywords., Results: Phytochemical analysis of C. nigrescens, P. africana and P. macrocarpa revealed the presence of some prominent bioactive compounds such as convallatoxin, 7,3,4-trihydroxy-3-methoxyflavanone and dioxane, respectively. Plant extracts and isolated compounds of these medicinal plants exhibited a wide range of ethnopharmacological activities including antimicrobial, anti-inflammatory, antioxidant, analgesic, cytotoxic, antimalarial, antipyretic, haematinic, hepato-protective, aphrodisiac and antihypertensive properties., Conclusion: The present review on C. nigrescens , P.africana and P. macrocarpa provided a credible summary of the ethnopharmacological research conducted on these medicinal plants till date. The data also highligted the potential therapeutic profiles of these plants in Ghana that could serve as foundation for future studies. Additionally, the information significantly supported the traditional and commercial use of these plants among the people., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Plasticity of phenotypic traits refers to an organism's ability to change in response to environmental stimuli. As a result, the response may alter an organism's physiological state, morphology, behavior, and phenotype. Phenotypic plasticity in cancer cells describes the considerable ability of cancer cells to transform phenotypes through non-genetic molecular signaling activities that promote therapy evasion and tumor metastasis via amplifying cancer heterogeneity. As a result of metastable phenotypic state transitions, cancer cells can tolerate chemotherapy or develop transient adaptive resistance. Therefore, new findings have paved the road in identifying factors and agents that inhibit or suppress phenotypic plasticity. It has also investigated novel multitargeted agents that may promise new effective strategies in cancer treatment. Despite the efficiency of conventional chemotherapeutic agents, drug toxicity, development of resistance, and high-cost limit their use in cancer therapy. Recent research has shown that small molecules derived from natural sources are capable of suppressing cancer by focusing on the plasticity of phenotypic responses. This systematic, comprehensive, and critical review analyzes the current state of knowledge regarding the ability of phytocompounds to target phenotypic plasticity at both preclinical and clinical levels. Current challenges/pitfalls, limitations, and future perspectives are also discussed., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Ethnopharmacological Relevance: Traditional Chinese medicine (TCM) meridian is the key theoretical guidance of prescription against tumor in clinical practice. However, there is no scientific and systematic verification of therapeutic action of herbs under meridians context. Several studies have determined the Chinese herbal medicine (CHM) phytochemicals for intrinsic attribute or meridians classification based on artificial intelligence (AI) tools. However, it is challenging to represent the complex molecular structures with large heterogeneity through the current technologies. In addition, the multiple correspondence between herbs and meridians has not been paid much attention., Aim of the Study: We aim to develop an AI framework to classify multi-target meridians through the topological structure of phytochemicals., Materials and Methods: A total of 354 anti-cancer herbs, their corresponding TCM meridians and 5471 ingredient compounds were collected from public databases of CancerHSP, ETCM, and Hit 2.0. The statistical analysis of herbal and compound datasets, clustering analysis of the associated cancers, and correlational analysis of meridian tropism were preliminary conducted. Then a deep learning (DL) hybrid model named GRMC consisting of graph convolutional network (GCN) and recurrent neural network (RNN) was employed to generate the meridian multi-label sequences based on molecular graph., Results: The curing herbs against tumors have tight relationships to lung, liver, stomach, and spleen meridians. These herbs behave different properties in curing certain cancer. Certain cancer types have co-occurrence such as ovarian, bladder and cervical cancer. Compounds have multitarget meridians with characteristics of higher-order correlations. Compared with the other state-of-the-art algorithms on the datasets and previous methods dealing with conventional fixed fingerprints of herbal compounds, the proposed GRMC has superior overall performance on testing dataset with the one error of 0.183, hamming loss of 0.112, mean averaged accuracy (MAA) of 0.855, mean averaged precision (MAP) of 0.891, mean averaged recall (MAR) of 0.812, and mean averaged F1 score (MAF) of 0.849., Conclusions: The proposed method can predict multi-targeted meridians through neural graph features in herbal compounds and outperforms several comparison methods. It could provide a basis for understanding the molecular scientific evidence of TCM meridians., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Angiogenesis, a multistep process, involves sprouting of new vessels from the pre-existing vessels in response to a stimulus in its microenvironment. Normally, angiogenesis is important for tissue maintenance and homeostasis, however it is also known to be associated with various pathologies, including cancer. Importantly, neovascularization is very crucial for tumors to grow and metastasize since it allows delivery of oxygen and nutrients as well as promotes tumor cell dissemination to distant sites. Activation of angiogenic switch is a consequence of imbalance in pro- as well as anti-angiogenic factors, that are immensely impacted by reactive oxygen species and epigenetic regulation. Several reports have suggested that angiogenic inhibitors significantly inhibit tumor growth. Therefore, anti-angiogenic therapy has gained substantial attention and has been considered a rational approach in cancer therapeutics. In this line, several anti- angiogenic drugs have been approved, however, their long term usage caused several side effects. In view of this, researchers switched to plant-based natural compounds for identifying safe and cost-effective anti-angiogenic drugs. Of note, various phytochemicals have been evaluated to reduce tumor growth by inhibiting tumor-induced angiogenesis. Moreover, the implication of nano-carriers to enhance the bioavailability of phytochemicals has proven to be more efficient anti-cancer agents. The present review highlights the existing knowledge on tumor-induced neovascularization and its regulation at the epigenetic level. Further, we emphasize the inhibitory effect of phytochemicals on tumor- induced angiogenesis that will open up new avenues in cancer therapeutics., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Quercetin is a natural flavonoid with various pharmacological actions such as anti-inflammatory, antioxidant, antimicrobial, anticancer, antiviral, antidiabetic, cardioprotective, neuroprotective, and antiviral activities. Looking at these enormous potentials, researchers have explored how they can be used to manage numerous cancers. It's been studied for cancer management due to its anti-angiogenesis, anti-metastatic, and antiproliferative mechanisms. Despite having these proven pharmacological activities, the clinical use of quercetin is limited due to its first-- pass metabolism, poor solubility, and bioavailability. To address these shortcomings, researchers have fabricated various nanocarriers-based formulations to fight cancer. The present review overshadows the pharmacological potential, mechanisms, and application of nanoformulations against different cancers. Teaser: Explore the potential of Quercetin, a natural flavonoid with diverse pharmacological activities, and its nanoformulations in managing various cancers., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The use of natural bioactive constituents from various food sources for anticancer purposes has become increasingly popular worldwide. Broccoli ( Brassica oleracea var. italica ) is on the top of the consumed vegetables by the masses. Its raw matrix contains a plethora of phytochemicals, such as glucosinolates and phenolic compounds, along with rich amounts of vitamins, and minerals. Consumption of broccoli-derived phytochemicals provides strong antioxidant effects, particularly due to its sulforaphane content, while modulating numerous molecules involved in cell cycle regulation, control of apoptosis, and tuning enzyme activity. Thus, the inclusion of broccoli in the daily diet lowers the susceptibility to developing cancers. Numerous studies have underlined the undisputable role of broccoli in the diet as a chemopreventive raw food, owing to the content in sulforaphane, an isothiocyanate produced as a result of hydrolysis of precursor glucosinolates called glucoraphanin. This review will provide evidence supporting the specific role of fresh florets and sprouts of broccoli and its key bioactive constituents in the prevention and treatment of different cancers; a number of studies carried out in the in vitro and in vivo conditions as well as clinical trials were analyzed.

Annually, a significant number of individuals succumb to cancer, an anomalous cellular condition characterized by uncontrolled cellular proliferation and the emergence of highly perilous tumors. Identifying underlying molecular mechanism(s) driving disease progression has led to various inventive therapeutic approaches, many of which are presently under pre-clinical and/or clinical trials. Over the recent years, numerous alternative strategies for addressing cancer have also been proposed and put into practice. This article delineates the modern therapeutic drugs employed in cancer treatment and their associated toxicity. Due to inherent drug toxicity associated with most modern treatments, demand rises for alternative therapies and phytochemicals with minimal side effects and proven efficacy against cancer. Analogs of taxol, Vinca alkaloids like vincristine and vinblastine, and podophyllotoxin represent a few illustrative examples in this context. The phytochemicals often work by modifying the activity of molecular pathways that are thought to be involved in the onset and progression of cancer. The principal objective of this study is to provide an overview of our current understanding regarding the pharmacologic effects and molecular targets of the active compounds found in natural products for cancer treatment and collate information about the recent advancements in this realm. The authors' interest in advancing the field of phytochemical research stems from both the potential of these compounds for use as drugs as well as their scientific validity. Accordingly, the significance of herbal formulations is underscored, shedding light on anticancer phytochemicals that are sought after at both pre-clinical and clinical levels, with discussion on the opportunities and challenges in pre-clinical and clinical cancer studies., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Immunotherapy is a newly emerging and effective approach to treating cancer. However, there are many challenges associated with using checkpoint inhibitors in this treatment strategy. The component of the tumor microenvironment plays a crucial role in antitumor immune response, regulating tumor immune surveillance and immunological evasion. Natural products/phytochemicals can modulate the tumor microenvironment and function as immunomodulatory agents. In clinical settings, there is a strong need to develop synergistic combination regimens using natural products that can effectively enhance the therapeutic benefits of immune checkpoint inhibitors relative to their effectiveness as single therapies. The review discusses immunotherapy, its side effects, and a summary of evidence suggesting the use of natural products to modulate immune checkpoint pathways., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Chemotherapy is the mainstay of cancer treatment, bringing patients optimism about recurrence and survival. However, the clinical effectiveness of chemotherapeutic drugs is frequently jeopardized by their intrinsic toxicity, resulting in side effects affecting the quality of life of cancer patients. This analysis explores the ethnopharmacological impact of phytopharmaceuticals, highlighting their traditional use in many cultures. The present study, which takes its cues from indigenous knowledge, aims to close the knowledge gap between traditional medicine and modern medicine in reducing the toxicities of chemotherapy treatments., Aim: The present in-depth study aims to highlight the current research and upcoming developments in phytopharmaceuticals for reducing the toxicity of chemotherapeutic drugs. Further, we address the mechanisms through which phytopharmaceuticals may reduce chemotherapy-induced side effects that include nausea, vomiting, myelosuppression, nephropathy, neuropathy, and cardiotoxicity using data from a variety of preclinical and clinical investigations., Materials and Methods: The literature search was carried out by employing search engines such as PubMed and Google Scholar with keywords such as cancer, chemotherapy, CNS toxicity, hematopoietic toxicity, renal toxicity, GI toxicity, CNS toxicity, and phytopharmaceuticals., Results: Bioactive chemicals found in plants, such as fruits, vegetables, herbs, and spices, are being studied for their capacity to improve the safety and acceptability of chemotherapy regimens. The current review also dives into the investigation of phytopharmaceuticals as adjuvant medicines in cancer treatment, which is a viable path for addressing the pressing need to lessen chemotherapy-induced toxicities., Conclusion: The present review revealed that the potential of phytopharmaceuticals in alleviating chemotherapeutic drug toxicities would pave the way for better cancer treatment and patient outcomes, harmonizing with the larger trend towards personalized and holistic approaches to chemotherapy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Over the years, natural compounds have become a significant advancement in cancer treatment, primarily due to their effectiveness, safety, bio-functionality, and wide range of molecular structures. They are now increasingly preferred in drug discovery due to these attributes. These compounds, whether occurring naturally or with synthetic modifications, find applications in various fields like biology, medicine, and engineering. While chemotherapy has been a successful method for treating cancer, it comes with systemic toxicity. To address this issue, researchers and medical practitioners are exploring the concept of combinational chemotherapy. This approach aims to reduce toxicity by using a mix of natural substances and their derivatives in clinical trials and prescription medications. Among the most extensively studied natural anticancer compounds are quercetin, curcumin, vincristine, and vinblastine. These compounds play crucial roles as immunotherapeutics and chemosensitizers, both as standalone treatments and in combination therapies with specific mechanisms. This review article provides a concise overview of the functions, potentials, and combinations of natural anticancer compounds in cancer treatment, along with their mechanisms of action and clinical applications., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Cancer remains the leading cause of death and rapidly evolving disease worldwide. The understanding of disease pathophysiology has improved through advanced research investigation, and several therapeutic strategies are being used for better cancer treatment. However, the increase in cancer relapse and metastatic-related deaths indicate that available therapies and clinically approved chemotherapy drugs are not sufficient to combat cancer. Further, the constant crosstalk between tumor cells and the tumor microenvironment (TME) is crucial for the development, progression, metastasis, and therapeutic response to tumors. In this regard, phytochemicals with multimodal targeting abilities can be used as an alternative to current cancer therapy by inhibiting cancer survival pathways or modulating TME. However, due to their poor pharmacokinetics and low bioavailability, the success of phytochemicals in clinical trials is limited. Therefore, developing phytochemical-based nanomedicine or phytonanomedicine can improve the pharmacokinetic profile of these phytochemicals. Herein, the molecular characteristics and pharmacological insights of the proposed phytonanomedicine in cancer therapy targeting tumor tissue and altering the characteristics of cancer stem cells, chemoresistance, TME, and cancer immunity are well discussed. Further, we have highlighted the clinical perspective and challenges of phytonanomedicine in filling the gap in potential cancer therapeutics using various nanoplatforms. Overall, we have discussed how clinical success and pharmacological insights could make it more beneficial to boost the concept of nanomedicine in the academic and pharmaceutical fields to counter cancer metastases and drug resistance.

The high incidence of oral cancer combined with excessive treatment cost underscores the need for novel oral cancer preventive and therapeutic options. The value of natural agents, including plant secondary metabolites (phytochemicals), in preventing carcinogenesis and representing expansive source of anticancer drugs have been established. While fragmentary research data are available on antioral cancer effects of phytochemicals, a comprehensive and critical evaluation of the potential of these agents for the prevention and intervention of human oral malignancies has not been conducted according to our knowledge. This study presents a complete and critical analysis of current preclinical and clinical results on the prevention and treatment of oral cancer using phytochemicals. Our in-depth analysis highlights anticancer effects of various phytochemicals, such as phenolics, terpenoids, alkaloids, and sulfur-containing compounds, against numerous oral cancer cells and/or in vivo oral cancer models by antiproliferative, proapoptotic, cell cycle-regulatory, antiinvasive, antiangiogenic, and antimetastatic effects. Bioactive phytochemicals exert their antineoplastic effects by modulating various signaling pathways, specifically involving the epidermal growth factor receptor, cytokine receptors, toll-like receptors, and tumor necrosis factor receptor and consequently alter the expression of downstream genes and proteins. Interestingly, phytochemicals demonstrate encouraging effects in clinical trials, such as reduction of oral lesion size, cell growth, pain score, and development of new lesions. While most phytochemicals displayed minimal toxicity, concerns with bioavailability may limit their clinical application. Future directions for research include more in-depth mechanistic in vivo studies, administration of phytochemicals using novel formulations, investigation of phytocompounds as adjuvants to conventional treatment, and randomized clinical trials., (© 2023 Wiley Periodicals LLC.)

Since ancient times, dietary phytochemicals are known for their medicinal properties. They are broadly classified into polyphenols, terpenoids, alkaloids, phytosterols, and organosulfur compounds. Currently, there is considerable interest in their potential health effects against various diseases, including lung cancer. Lung cancer is the leading cause of cancer deaths with an average of five-year survival rate of lung cancer patients limited to just 14%. Identifying potential early molecular biomarkers of pre-malignant lung cancer cells may provide a strong basis to develop early cancer detection and interception methods. In this review, we will discuss molecular changes, including genetic alterations, inflammation, signal transduction pathways, redox imbalance, epigenetic and proteomic signatures associated with initiation and progression of lung carcinoma. We will also highlight molecular targets of phytochemicals during lung cancer development. These targets mainly consist of cellular signaling pathways, epigenetic regulators and metabolic reprogramming. With growing interest in natural products research, translation of these compounds into new cancer prevention approaches to medical care will be urgently needed. In this context, we will also discuss the overall pharmacokinetic challenges of phytochemicals in translating to humans. Lastly, we will discuss clinical trials of phytochemicals in lung cancer patients., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Anthocyanins are colored polyphenolic compounds that belong to the flavonoids family and are largely present in many vegetables and fruits. They have been used in traditional medicine in many cultures for a long time. The most common and abundant anthocyanins are those presenting an O-glycosylation at C-3 (C ring) of the flavonoid skeleton to form -O-β-glucoside derivatives. The present comprehensive review summarized recent data on the anticancer properties of cyanidings along with natural sources, phytochemical data, traditional medical applications, molecular mechanisms and recent nanostrategies to increase the bioavailability and anticancer effects of cyanidins. For this analysis, in vitro, in vivo and clinical studies published up to the year 2022 were sourced from scientific databases and search engines such as PubMed/Medline, Google scholar, Web of Science, Scopus, Wiley and TRIP database. Cyanidins' antitumor properties are exerted during different stages of carcinogenesis and are based on a wide variety of biological activities. The data gathered and discussed in this review allows for affirming that cyanidins have relevant anticancer activity in vitro, in vivo and clinical studies. Future research should focus on studies that bring new data on improving the bioavailability of anthocyanins and on conducting detailed translational pharmacological studies to accurately establish the effective anticancer dose in humans as well as the correct route of administration., Competing Interests: Conflict of interest statement The authors declare that they have no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

A biological process called epithelial-mesenchymal transition (EMT) allows epithelial cells to change into mesenchymal cells and acquire some cancer stem cell properties. EMT contributes significantly to the metastasis, invasion, and development of treatment resistance in cancer cells. Current research has demonstrated that phytochemicals are emerging as a potential source of safe and efficient anti-cancer medications. Phytochemicals could disrupt signaling pathways related to malignant cell metastasis and drug resistance by suppressing or reversing the EMT process. In this review, we briefly describe the pathophysiological properties and the molecular mechanisms of EMT in the progression of cancers, then summarize phytochemicals with diverse structures that could block the EMT process in different types of cancer. Hopefully, these will provide some guidance for future research on phytochemicals targeting EMT.

Cancer therapy with clinically established anticancer drugs is frequently hampered by the development of drug resistance of tumors and severe side effects in normal organs and tissues. The demand for powerful, but less toxic, drugs is high. Phytochemicals represent an important reservoir for drug development and frequently exert less toxicity than synthetic drugs. Bioinformatics can accelerate and simplify the highly complex, time-consuming, and expensive drug development process. Here, we analyzed 375 phytochemicals using virtual screenings, molecular docking, and in silico toxicity predictions. Based on these in silico studies, six candidate compounds were further investigated in vitro. Resazurin assays were performed to determine the growth-inhibitory effects towards wild-type CCRF-CEM leukemia cells and their multidrug-resistant, P-glycoprotein (P-gp)-overexpressing subline, CEM/ADR5000. Flow cytometry was used to measure the potential to measure P-gp-mediated doxorubicin transport. Bidwillon A, neobavaisoflavone, coptisine, and z-guggulsterone all showed growth-inhibitory effects and moderate P-gp inhibition, whereas miltirone and chamazulene strongly inhibited tumor cell growth and strongly increased intracellular doxorubicin uptake. Bidwillon A and miltirone were selected for molecular docking to wildtype and mutated P-gp forms in closed and open conformations. The P-gp homology models harbored clinically relevant mutations, i.e., six single missense mutations (F336Y, A718C, Q725A, F728A, M949C, Y953C), three double mutations (Y310A-F728A; F343C-V982C; Y953A-F978A), or one quadruple mutation (Y307C-F728A-Y953A-F978A). The mutants did not show major differences in binding energies compared to wildtypes. Closed P-gp forms generally showed higher binding affinities than open ones. Closed conformations might stabilize the binding, thereby leading to higher binding affinities, while open conformations may favor the release of compounds into the extracellular space. In conclusion, this study described the capability of selected phytochemicals to overcome multidrug resistance.

Angelica species have been traditionally used for their medicinal properties. Recent studies have suggested their potential use as anticancer agents, making them an area of interest for further research. The review aims to summarize the current understanding of the potential anticancer effects of Angelica species and to provide insights for further research in this area. We searched for "Angelica" related information on Google Scholar, PubMed, ScienceDirect, Wiley, Science Citation Index Finder, and Springer link by searching keywords such as "Angelica," "Angelica phytochemical," "Angelica antitumor effect," "Angelica molecular mechanisms," and "Angelica clinical application." Included articles focused on the Angelica plant's anticancer properties and clinical studies, while non-cancer-related biological or phytochemical investigations were excluded. We conducted a comprehensive search of books, journals, and databases published between 2001 and 2023, identifying 186 articles for this narrative review. The articles were analyzed for their potential anticancer properties and therapeutic applications. Active compounds in the Angelica genus, such as coumarins, furanocoumarins, phthalides, and polysaccharides, exhibit anticancer properties through various mechanisms. Specific species, like A. archangelica, Angelica sinensis, A. gigas, and A. ksiekie, have the potential as anticancer agents by targeting cellular pathways, generating reactive oxygen species, and inducing apoptotic cell death. Further research into the properties of the Angelica genus is needed for developing new treatments for cancer. Phytochemicals from Angelica species possess potential as anticancer agents, requiring further research for the development of effective, low-cost, and low-toxicity cancer treatments compared to synthetic antitumor drugs., (© 2023 John Wiley & Sons Ltd.)

Magnolin is a naturally occurring, multi-bioactive lignan molecule with inherent anticancer effects. This study aims to summarize the botanical origins and anticancer properties of magnolin. For this, a recent (as of March 2023) literature review was conducted using various academic search engines, including PubMed, Springer Link, Wiley Online, Web of Science, Science Direct, and Google Scholar. All the currently available information about this phytochemical and its role in various cancer types has been gathered and investigated. Magnolin is a compound found in many different plants. It has been demonstrated to have anticancer activity in numerous experimental models by inhibiting the cell cycle (G1 and G2/M phase); inducing apoptosis; and causing antiinvasion, antimetastasis, and antiproliferative effects via the modulation of several pathways. In conclusion, magnolin showed robust anticancer activity against many cancer cell lines by altering several cancer signaling pathways in various non- and pre-clinical experimental models, making it a promising plant-derived chemotherapeutic option for further clinical research.

Phytochemicals are a non-nutritive substances that are present in plants and contribute significantly to their flavor and color. These biologically active compounds are classified into five major groups, namely phenolics, carotenoids, organosulfur compounds, nitrogen-containing compounds, and alkaloids, and are known for their potential health benefits in the prevention of various diseases, including cancer. The purpose of this review article is to explore the potential therapeutic benefits of the dietary phytochemicals, such as flavonoids, phenolic acids, phytosterols, carotenoids, and stilbenes, in cancer treatment and prevention based on the epidemiological studies and clinical trials. Although the majority of epidemiological studies report a significant advantage of the heightened phytochemical consumption and increased serum levels of these compounds, linking increased exposure with a lower cancer risk across most cancer types, these effects could not be replicated in the most available clinical trials. In fact, many of these trials were withdrawn early due to a lack of evidence and/or risk of harm. Despite the strong anticancer effect of phytochemicals, as well as their proven efficacy in multiple epidemiological studies, there is still a great need for human studies and clinical trials, with great caution regarding the safety measures. This review article provides an overview of the epidemiological and clinical evidence supporting the potential chemopreventive and anticancer properties of phytochemicals, with a focus on the need for further research in this area.

Natural plant phytochemicals are effective against different types of diseases, including cancer. Curcumin, a powerful herbal polyphenol, exerts inhibitory effects on cancer cell proliferation, angiogenesis, invasion, and metastasis through interaction with different molecular targets. However, the clinical use of curcumin is limited due to poor solubility in water and metabolism in the liver and intestine. The synergistic effects of curcumin with some phytochemicals such as resveratrol, quercetin, epigallocatechin-3-gallate, and piperine can improve its clinical efficacy in cancer treatment. The present review specifically focuses on anticancer mechanisms related to the co-administration of curcumin with other phytochemicals, including resveratrol, quercetin, epigallocatechin-3-gallate, and piperine. According to the molecular evidence, the phytochemical combinations exert synergistic effects on suppressing cell proliferation, reducing cellular invasion, and inducing apoptosis and cell cycle arrest. This review also emphasizes the significance of the co-delivery vehicles-based nanoparticles of such bioactive phytochemicals that could improve their bioavailability and reduce their systemic dose. Further high-quality studies are needed to firmly establish the clinical efficacy of the phytochemical combinations., (© 2023 John Wiley & Sons Ltd.)

Cancer is a hard-to-treat disease with a high reoccurrence rate that affects health and lives globally. The condition has a high occurrence rate and is the second leading cause of mortality after cardiovascular disorders. Increased research and more profound knowledge of the mechanisms contributing to the disease's onset and progression have led to drug discovery and development. Various drugs are on the market against cancer; however, the drugs face challenges of chemoresistance. The other major problem is the side effects of these drugs. Therefore, using complementary and additional medicines from natural sources is the best strategy to overcome these issues. The naturally occurring phytochemicals are a vast source of novel drugs against various ailments. The modes of action by which phytochemicals show their anti-cancer effects can be the induction of apoptosis, the onset of cell cycle arrest, kinase inhibition, and the blocking of carcinogens. This review aims to describe different phytochemicals, their classification, the role of phytochemicals as anti-cancer agents, the mode of action of phytochemicals, and their role in various types of cancer.

A natural α-1,6-glucan named BBWPW was identified from black beans. Cell viability assay showed that BBWPW inhibited the proliferation of different cancer cells, especially HeLa cells. Flow cytometry analysis indicated that BBWPW suppressed the HeLa cell cycle in the G2/M phase. Consistently, RT-PCR experiments displayed that BBWPW significantly impacts the expression of four marker genes related to the G2/M phase, including p21 , CDK1 , Cyclin B1 , and Survivin . To explore the molecular mechanism of BBWPW to induce cell cycle arrest, a transcriptome-based target inference approach was utilized to predict the potential upstream pathways of BBWPW and it was found that the PI3K-Akt and MAPK signal pathways had the potential to mediate the effects of BBWPW on the cell cycle. Further experimental tests confirmed that BBWPW increased the expression of BAD and AKT and decreased the expression of mTOR and MKK3. These results suggested that BBWPW could regulate the PI3K-Akt and MAPK pathways to induce cell cycle arrest and ultimately inhibit the proliferation of HeLa cells, providing the potential of the black bean glucan to be a natural anticancer drug.

In the present study, the binding affinity of 52 bioactive secondary metabolites from Wedelia trilobata towards the anti-apoptotic B-cell lymphoma-2 (Bcl-2) protein (PDB: 2W3L) structure was identified by using in silico molecular docking and molecular dynamics simulation. The molecular docking results demonstrated that the binding energies of docked compounds with Bcl-2 protein ranged from -5.3 kcal/mol to -10.1 kcal/mol. However, the lowest binding energy (-10.1 kcal/mol) was offered by Friedelin against Bcl-2 protein when compared to other metabolites and the standard drug Obatoclax (-8.4 kcal/mol). The molecular dynamics simulations revealed that the Friedelin-Bcl-2 protein complex was found to be stable throughout the simulation period of 100 ns. Overall, the predicted Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) properties of Friedelin are relatively better than Obatoclax, with the most noticeable differences in many parameters where Friedelin has no AMES toxicity, hepatotoxicity, and skin sensitization. The ADMET profiling of selected compounds supported their in silico drug-likeness properties. Based on the computational analyses, the present study concluded that Friedelin of W. trilobata was found to be the potential inhibitor of the Bcl-2 protein, which merits attention for further in vitro and in vivo studies before clinical trials.

Plant secondary metabolites, known as phytochemicals, have recently gained much attention in light of the "circular economy", to reutilize waste products deriving from agriculture and food industry. Phytochemicals are known for their onco-preventive and chemoprotective effects, among several other beneficial properties. Apple phytochemicals have been extensively studied for their effectiveness in a wide range of diseases, cancer included. This review aims to provide a thorough overview of the main studies reported in the literature concerning apple phytochemicals, mostly polyphenols, in cancer prevention. Although there are many different mechanisms targeted by phytochemicals, the Nrf2 and NF-κB signaling pathways are the ones this review will be focused on, highlighting also the existing crosstalk between these two systems.

Apoptosis is the elimination of functionally non-essential, neoplastic, and infected cells via the mitochondrial pathway or death receptor pathway. The process of apoptosis is highly regulated through membrane channels and apoptogenic proteins. Apoptosis maintains cellular balance within the human body through cell cycle progression. Loss of apoptosis control prolongs cancer cell survival and allows the accumulation of mutations that can promote angiogenesis, promote cell proliferation, disrupt differentiation, and increase invasiveness during tumor progression. The apoptotic pathway has been extensively studied as a potential drug target in cancer treatment. However, the off-target activities of drugs and negative implications have been a matter of concern over the years. Phytochemicals (PCs) have been studied for their efficacy in various cancer cell lines individually and synergistically. The development of nanoparticles (NPs) through green synthesis has added a new dimension to the advancement of plant-based nanomaterials for effective cancer treatment. This review provides a detailed insight into the fundamental molecular pathways of programmed cell death and highlights the role of PCs along with the existing drugs and plant-based NPs in treating cancer by targeting its programmed cell death (PCD) network.

Metastasis is a multi-step phenomenon during cancer development leading to the propagation of cancer cells to distant organ(s). According to estimations, metastasis results in over 90% of cancer-associated death around the globe. Long non-coding RNAs (LncRNAs) are a group of regulatory RNA molecules more than 200 base pairs in length. The main regulatory activity of these molecules is the modulation of gene expression. They have been reported to affect different stages of cancer development including proliferation, apoptosis, migration, invasion, and metastasis. An increasing number of medical data reports indicate the probable function of LncRNAs in the metastatic spread of different cancers. Phytochemical compounds, as the bioactive agents of plants, show several health benefits with a variety of biological activities. Several phytochemicals have been demonstrated to target LncRNAs to defeat cancer. This review article briefly describes the metastasis steps, summarizes data on some well-established LncRNAs with a role in metastasis, and identifies the phytochemicals with an ability to suppress cancer metastasis by targeting LncRNAs.

Although Annona squamosa Linn. (Annonaceae) has been used in traditional medicine and is known to have several pharmacological properties, its impact on EGFR kinase has not been fully investigated. An assay (biochemical) was used to govern the potential of different A. squamosa seed extracts to scavenge free radicals in petroleum ether, acetone, ethanol, and methanol. We also tested A. squamosa leaf extracts for their ability to inhibit the growth of HEK 293, MCF7, and HepG2 cell lines. The PSE, ASE, ESE, and MSE all contained anti-cancer substances like anethole, cyclopentane, 1,1,3-trimethyl, and phosphonate oxide tributyl, according to phytochemical analysis. ESE extracts from A. squamosa seeds have been selected based on free radical generation probabilities, cytotoxicity studies, and phytochemical analysis. Subsequent insilico studies have been conducted, and the results have shown that interactions between compounds present in ESE extracts and the EGFR kinase are what give these compounds their inhibitory effects. Preliminary phytochemical and pharmacological activities were studied and reported. A. squamosa ESE extracts inhibited the growth of MCF7 cells, and a pharmacokinetic study showed that the compounds anethole, cyclopentane, 1,1,3-trimethyl, and phosphonium oxide tributyl had few undesirable side effects. These substances can be used to both prevent and treat cancer diseases.

The present study was focused on the screening of phytochemicals, their quantitative estimation and analysis by LC-MS profile, and antiproliferative efficacy of the aqueous-ethanolic extracts of the microalgae, Chlorochromonas danica isolated from the freshwater body Tavanampalli. The aqueous-ethanol extract of Chlorochromonas danica showed the presence of flavonoids, phenols, and proteins. The total flavonoid content, total phenol content, and total protein content were determined to be 158.65 mg of quercetin equivalent, 15.75 mg of gallic acid equivalent, and 134.65 mg/g dry weight of the extract, respectively. The LC-MS analysis confirmed the presence of several major bioactive molecules including L-Histidine, D-glutamine, L-aspartic acid, adenine, adenosine, cotinine, guanine hypoxanthine, L-glutamic acid, nicotinamide, 4-Hydroxycoumarin, and Stearamide. The aqueous-ethanol extract of Chlorochromonas danica exhibited an IC 50 values of 63.34 µg, 279.29 µg, 125.42 µg, 90.56 µg, and 95.58 µg against A375, A549, HeLa, HepG2, and HT29 cell lines respectively, compared to the positive control cisplatin with IC 50 values of 3.56 µg, 4.65 µg, 3.88 µg, 4.87 µg, and 7.23 µg respectively. These data suggest that Chlorochromonas danica remains a promising drug candidate for the treatment of cancers, particularly melanoma (A375 cell line) that can be considered for purification of antiproliferative compound and further clinical trials for the discovery of novel antiproliferative drugs from cost-effective sources., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Cancer and diabetes mellitus are served as typical life-threatening diseases with common risk factors. Developing therapeutic measures in cancers and diabetes have aroused attention for a long time. However, the problems with conventional treatments are in challenge, including side effects, economic burdens, and patient compliance. It is essential to secure safe and efficient therapeutic methods to overcome these issues. As an alternative method, antioxidant and pro-oxidant properties of phytochemicals from edible plants have come to the fore. Phytochemicals are naturally occurring compounds, considered promising agent applicable in treatment of various diseases with beneficial effects. Either antioxidative or pro-oxidative activity of various phytochemicals were found to contribute to regulation of cell proliferation, differentiation, cell cycle arrest, and apoptosis, which can exert preventive and therapeutic effects against cancer and diabetes. In this article, the antioxidant or pro-oxidant effects and underlying mechanisms of flavonoids, alkaloids, and saponins in cancer or diabetic models demonstrated by the recent studies are summarized.