Phytochemicals In Cancer Prevention Research Articles

Exploring the Potential of Dietary Phytochemicals in Cancer Prevention: A Comprehensive Review

Exploring the Potential of Dietary Phytochemicals in Cancer Prevention: A Comprehensive Review

Emerging Potential of Momordica’s Bioactive Phytochemicals in Cancer Prevention and Therapy

Worldwide, cancer incidence and mortality are rising quickly. Cancer remains the biggest cause of death despite advances in therapy. Plants produce bioactive phytochemicals, and as a result, the bioactive elements have long been the focus of cancer research, both for medication discovery and for the discovery of alternative chemo-preventive methods. The medicinal plant Momordica charantia or bitter melon contains a wide variety of phytochemicals, such as triterpenoids, triterpene glycosides, phenolic acids, flavonoids, lectins, sterols, and proteins. In many pre-clinical systems, the Momordica charantia extract exhibits an anti-cancer action against various malignancies. The bioactive components of the extract play a significant role in its anti-cancer properties. With an emphasis on underlying molecular pathways, we address the roles of Momordica's known bioactive components in several cancer models in this review. Through the inhibition of cancer cell proliferation and induction of cell death, several of active ingredients exhibit cancer prevention and therapeutic effects, at least in in-vitro models. Mechanistically examining the active components in pre-clinical systems may reveal a novel approach to cancer treatment.

Role of Dietary Phytochemicals in Targeting Human miRNAs for Cancer Prevention and Treatment.

MicroRNAs (miRNAs - ~22 nucleotides) are a type of non-coding RNAs that are involved in post-transcriptional gene silencing. They are known to regulate gene expression in diverse biological processes, such as apoptosis, development, and differentiation. Several studies have demonstrated that cancer initiation and progression are highly regulated by miRNA expression. The nutrients present in the diet may regulate the different stages of carcinogenesis. Interestingly, plant-based foods, like fruits and vegetables, have been shown to play a significant role in cancer prevention. Phytochemicals are bioactive compounds derived from plant sources, and they have been shown to have antiinflammatory, antioxidant, and anticancer properties. Recent findings suggest that dietary phytochemicals, such as genistein, resveratrol, and curcumin, exert significant anticancer effects by regulating various miRNAs. In this review, we focus on the role of dietary phytochemicals in cancer prevention and treatment through the modulation of miRNA expression.

Role of autophagic response induced by major phytochemicals in cancer prevention and treatment

Journal of Cancer Metastasis and Treatment is an open access journal, focusing on basic and clinical studies related to cancer cell, cell biology, oncology, radiation therapy and radiology, obstetrics and gynecology, pediatrics, surgery, hematology, neuro-oncology, etc.

Nutraceuticals: Role of phytochemicals in cancer prevention

Nutraceuticals: Role of phytochemicals in cancer prevention

Role of Phytochemicals in Cancer Prevention.

The use of synthetic, natural, or biological agents to minimize the occurrence of cancer in healthy individuals is defined as cancer chemoprevention. Chemopreventive agents inhibit the development of cancer either by impeding DNA damage, which leads to malignancy or by reversing or blocking the division of premalignant cells with DNA damage. The benefit of this approach has been demonstrated in clinical trials of breast, prostate, and colon cancer. The continuous increase in cancer cases, failure of conventional chemotherapies to control cancer, and excessive toxicity of chemotherapies clearly demand an alternative approach. The first trial to show benefit of chemoprevention was undertaken in breast cancer patients with the use of tamoxifen, which demonstrated a significant decrease in invasive breast cancer. The success of using chemopreventive agents for protecting the high risk populations from cancer indicates that the strategy is rational and promising. Dietary components such as capsaicin, cucurbitacin B, isoflavones, catechins, lycopenes, benzyl isothiocyanate, phenethyl isothiocyanate, and piperlongumine have demonstrated inhibitory effects on cancer cells indicating that they may serve as chemopreventive agents. In this review, we have addressed the mechanism of chemopreventive and anticancer effects of several natural agents.

Combinatorial Epigenetics Impact of Polyphenols and Phytochemicals in Cancer Prevention and Therapy.

Polyphenols are potent micronutrients that can be found in large quantities in various food sources and spices. These compounds, also known as phenolics due to their phenolic structure, play a vital nutrient-based role in the prevention of various diseases such as diabetes, cardiovascular diseases, neurodegenerative diseases, liver disease, and cancers. However, the function of polyphenols in disease prevention and therapy depends on their dietary consumption and biological properties. According to American Cancer Society statistics, there will be an expected rise of 23.6 million new cancer cases by 2030. Due to the severity of the increased risk, it is important to evaluate various preventive measures associated with cancer. Relatively recently, numerous studies have indicated that various dietary polyphenols and phytochemicals possess properties of modifying epigenetic mechanisms that modulate gene expression resulting in regulation of cancer. These polyphenols and phytochemicals, when administrated in a dose-dependent and combinatorial-based manner, can have an enhanced effect on epigenetic changes, which play a crucial role in cancer prevention and therapy. Hence, this review will focus on the mechanisms of combined polyphenols and phytochemicals that can impact various epigenetic modifications such as DNA methylation and histone modifications as well as regulation of non-coding miRNAs expression for treatment and prevention of various types of cancer.

Polyphenols and other Phytochemicals in Cancer Prevention and Management

Phenolic compounds and other phytochemicals are significant resources for drug discovery and development. Plant‐derived natural products have contributed in preventing and managing oxidative stress, and in cancer therapeutics. Recent reports indicate that 83% of new anti‐cancer agents are of natural product origin. The aim of this study was to assess the content and properties of bioactive phytochemicals in water, ethanol, methanol, acetone, and dichloromethane extracts of Prunus africana, Pausinystalia yohimbe, Moringa oleifera, Momordica charantia and Orthero spp, and test their therapeutic effect on a wide range of diseases. In the first part of the study, the content of total polyphenols (TPC), flavonoids (TFC), carotenoid, anthocyanin, and antioxidant properties of the extracts of the different plant parts of these five plants were measured using the Folin‐Ciocalteu, 2,2‐diphenyl‐1‐picrylhydrazyl radical scavenging activity (DPPH), ferric reducing antioxidant power (FRAP), and 2,2′‐Azino‐bis(3‐ ethylbenzthiazoline‐6‐sulfonic acid) radical scavenging (ABTS) assays. For most samples, extraction yields were highest when either ethanol or methanol were used as extraction solvent. The FRAP values were in the range of 6.04 – 112.00 μM Fe2+/g, while the highest TPC and TFC were seen in the methanol extract of P. africana bark from Cameroon (1397.33 mg GAE/g) and acetone extract of M. charantia leaf (217.33 mg RU/g), respectively. The concentration required to obtain a 50% antioxidant effect (EC50) for the acetone and methanol extracts of P. africana bark (Cameroon), methanol and ethanol extracts of P. yohimbe leaf and the methanol extract of P. yohimbe root were comparable to that of ascorbic acid. Seven phenolic acids were identified in the extracts of P. africana and P. yohimbe using high performance liquid chromatography (HPLC). The most abundant phenolic acids were; vanillic acid (116.41 mg/g dry extract in P. yohimbe leaf methanol extract) and trans‐sinapic acid (102.22 mg/g dry extract in P. africana bark water extract). This study shows that these plants parts are valuable sources of natural polyphenols and antioxidants and their individual and/ synergistic effect may modulate cellular and signaling events involved in growth and invasion of cancer cells.Support or Funding InformationUSDA‐NIFADelaware State UniversityThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Role of Dietary Cancer-Preventive Phytochemicals in Pancreatic Cancer Stem Cells.

This article provides a brief overview of cancer-preventive phytochemicals specifically targeting pancreatic cancer (PC) stem cells for prevention and treatment. Cancer stem cells (CSCs) represent a small proportion of the total cells of a given tumor, and contribute to tumor growth, recurrence, metastasis, and treatment resistance. Many intertwined pathways, including hedgehog, Wnt Signaling, and NOTCH, have been shown to play a role in the formation of CSCs. Recently, numerous chemopreventive agents, such as genistein, (-)-epigallocatechin-3-gallate (EGCG), sulforaphane, curcumin, resveratrol, and quercetin, have been shown to target CSCs mediated through the inhibition of multiple signalling pathways, to avoid toxicity and the side effects of chemical compounds. A growing body of research suggests that CSCs are the drivers in treatment resistance, cancer recurrence, and metastasis, in addition to tumor initiation and heterogeneity. Patient survival depends on these CSCs, which are one cause of tumor recurrence after surgery and chemotherapy. Therefore, target selection; an improved understanding of CSC biology, the genetic and molecular profiles of CSCs, and their key signaling pathways, and; appropriate clinical trials endpoints that are designed to target CSCs will help in the development of drugs that will specifically target this small population of stem cells.

Potential Mechanisms of Action of Dietary Phytochemicals for Cancer Prevention by Targeting Cellular Signaling Transduction Pathways.

Cancer is a severe health problem that significantly undermines life span and quality. Dietary approach helps provide preventive, nontoxic, and economical strategies against cancer. Increased intake of fruits, vegetables, and whole grains are linked to reduced risk of cancer and other chronic diseases. The anticancer activities of plant-based foods are related to the actions of phytochemicals. One potential mechanism of action of anticancer phytochemicals is that they regulate cellular signal transduction pathways and hence affects cancer cell behaviors such as proliferation, apoptosis, and invasion. Recent publications have reported phytochemicals to have anticancer activities through targeting a wide variety of cell signaling pathways at different levels, such as transcriptional or post-transcriptional regulation, protein activation and intercellular messaging. In this review, we discuss major groups of phytochemicals and their regulation on cell signaling transduction against carcinogenesis via key participators, such as Nrf2, CYP450, MAPK, Akt, JAK/STAT, Wnt/β-catenin, p53, NF-κB, and cancer-related miRNAs.

Polyphenolic Phytochemicals in Cancer Prevention and Therapy: Bioavailability versus Bioefficacy.

Natural polyphenols are organic chemicals which contain phenol units in their structures. They show antitumor properties. However, a key problem is their short half-life and low bioavailability under in vivo conditions. Still, definitively demonstrating the human benefits of isolated polyphenolic compounds (alone or in combination) using modern scientific methodology has proved challenging. The most common discrepancy between experimental and clinical observations is the use of nonphysiologically relevant concentrations of polyphenols in mechanistic studies. Thus, it remains highly controversial how applicable underlying mechanisms are with bioavailable concentrations and biological half-life. The present Perspective analyses proposed antitumor mechanisms, in vivo reported antitumor effects, and possible mechanisms that may explain discrepancies between bioavailability and bioefficacy. Polyphenol metabolism and possible toxic side effects are also considered. Our main conclusion emphasizes that these natural molecules (and their chemical derivatives) indeed can be very useful, not only as cancer chemopreventive agents but also in oncotherapy.

Phytochemicals in Cancer Prevention: A Review of the Evidence

Context: Cancer generally is considered as a neoplastic disease with particular causative and etiologic factors as well as protective elements. Although it has remained difficult to treat, it is preventable. Recently, the interest in dietary phytochemicals intake has considerably increased for potential cancer chemoprevention. Evidence Acquisition: This report reviews the role of phytochemical consumption in cancer prevention based on publications from PubMed, Science direct, Google Scholar, and Scopus from the year 1996 onward using cancer, chemoprevention, phytochemical keywords. Results: Regular intake of phytochemicals has been demonstrated to prevent cancer during its different stages including initiation, promotion and progression. Considering the animal models, the second step is the main stage for cancer chemoprevention. Conclusions: The phytochemicals involved in chemoprevention can be categorized in different groups naming phenolics, carotenoid, alkaloids, organosulfur compounds and nitrogen-containing compounds. They are able to stop, postpone and reverse carcinogenesis by different mechanisms.

Inhibition of pancreatic cancer cell migration by plasma anthocyanins isolated from healthy volunteers receiving an anthocyanin-rich berry juice.

Pancreatic cancer is an aggressive cancer type, of which the most important characteristics are migration and metastasis. Anthocyanins (ACN) are discussed to be protective phytochemicals; however, up to now only scarce data are available regarding their effects on cancer prevention. In this study, we aimed to determine whether ACN and their metabolites from plasma (PAM), isolated from blood of healthy volunteers after ingestion of an ACN-rich juice, are effective in modulating cancer cell migration in vitro. PAM were isolated from blood of healthy volunteers (n=10) after consumption of an ACN-rich berry juice. Before ingestion (PAM0min) and after 60min (PAM60min), blood was taken and PAM were isolated from plasma by solid-phase extraction. Migration of pancreatic cancer cells PANC-1 and AsPC-1 was assayed in a Boyden chamber. The influence of PAM on cellular reactive oxygen species (ROS) or mitochondria-specific ROS was measured fluorimetrically. mRNA expression levels of matrix metalloproteinases (MMP-2 and MMP-9) and NF-κB mRNA were determined by real-time PCR. After application of PAM60min to PANC-1, we observed a reduced cell migration, which was associated with reduced levels of endogenously generated ROS concomitant with reduced NF-κB as well as MMP-2 and MMP-9 mRNA expression levels. In AsPC-1 cells, however, migration was not affected by PAM60min. It can be assumed that physiologically relevant ACN and their metabolites were able to inhibit pancreatic cancer cell migration in dependency of the phenotype of cells and may thus deserve further attention as potential bioactive phytochemicals in cancer prevention.

Phytochemicals in Cancer Prevention and Therapy.

Despite advances in modern medicine, cancer is still the major cause of mortality in both developing and developed countries. Search for safer and more effective chemoprevention and treatment strategy is a need for the improvement of patient care in the field. Prevention may be more effective and less costly because cancer is largely a preventable disease which could be attributed to a greater extent to lifestyle. Dietary phytochemicals have been used for the treatment of cancer throughout history due to their safety, low toxicity, and general availability. Population based studies suggest that a reduced risk of cancer is associated with high consumption of vegetables and fruits. Promising phytochemicals not only disrupt aberrant signaling pathways leading to cancer but also synergize with chemotherapy and radiotherapy. Thus, the cancer chemoprevention and therapeutic potential of naturally occurring phytochemicals are of great interest. In this special issue we have collected many interesting original research articles and reviews that provide solid evidence to support the application of phytochemicals or dietary agents in prevention and treatment of cancer. This special issue contains 3 review articles and 9 original peer-reviewed papers. A. M. Harrison et al. performed a systematic review of the biomedical literature for the use of phytochemicals for management of cancer therapy pain in human subjects; X.-Y. Chen et al. explored the molecular mechanisms underlying the antimetastatic activity of black rice anthocyanins and identified its molecular targets in HER2+ breast cancer cells; the study by Y. Zeng et al. reports that Southwest China (especially Yunnan and Tibet) is the center of lowest mortality of cancers in China based on coevolution between human's anticancer activities and functional foods from crop origin center; M. Sugata et al. studied the anti-inflammatory and anticancer activities of Taiwanese purple-fleshed sweet potatoes (Ipomoea batatas L. Lam.) extracts; R. Moo-Puc et al. investigated the antiproliferative activity of bonediol, an alkyl catechol isolated from the Mayan medicinal plant Bonellia macrocarpa against human prostate tumor cells; B. Moyo and S. Mukanganyama demonstrate the antiproliferative potential of T. welwitschii extract on Jurkat T cells; C.-J. Tai et al. report the potential of ethanolic extract of Taiwanofungus camphoratus (Antrodia camphorata) to enhance the cytotoxicity of cisplatin and doxorubicin on human hepatocellular carcinoma cells; G. Wang et al. explored the molecular mechanism of total flavonoids extracted from Cotinus coggygria against glioblastoma cancer in vitro and in vivo; M. N. Mallick et al. studied the anticancer activity of hydroalcoholic extract of Picrorhiza kurroa and its fractions; M. F. Abu Bakar et al. demonstrate that the Garcinia dulcis fruit extract induced cytotoxicity and apoptosis in HepG2 liver cancer cells; G. Weng et al. reported the curcumin enhanced busulfan-induced apoptosis in leukemia stem-like KG1a cells via downregulating the expression of survivin; S. Kumar and J. Kim in their review discuss potency and selectivity of PLK-1-targeted inhibitors and their molecular interactions with PLK-1 domains. In conclusion, this special issue discussed the potential anticancer phytochemicals and dietary agents, their molecular targets, and their mechanisms of actions. The understanding of molecular mechanism of a specific plant derived compound against a particular type of cancer will lead to the invention of novel drug and drug targets for therapeutic intervention.

Drink your prevention: beverages with cancer preventive phytochemicals.

Specific alimentary habits, including oriental and Mediterranean diets characterized by high consumption of vegetables, fruits, cereals and, for the Mediterranean diet, olive oil, are associated with a reduction of risk of cardiovascular diseases, type 2 diabetes, neurodegenerative diseases, and some cancers. Numerous beverages contain diverse natural compounds, termed phytochemicals, that have been reported to exert antitumor, antiangiogenic, and antioxidant properties. Here we review the chemopreventive and angiopreventive properties of selected phytochemicals found in common beverages: epigallocatechin(green tea), triterpenoids (citrus juices), resveratrol (red wine), xanthohumol (beer), procyanidin (chocolate), and caffeine (coffee), focusing on their molecular mechanisms, providing "ready to drink" prevention approaches.

Impact of soy isoflavones on the epigenome in cancer prevention.

Isoflavones (IF) such as genistein are cancer preventive phytochemicals found in soy and other legumes. Epidemiological studies point to a reduced risk for hormone‑dependent cancers in populations following a typical Asian diet rich in soy products. IF act as phytoestrogens and prevent tumorigenesis in rodent models by a broad spectrum of bioactivities. During the past 10 years, IF were shown to target all major epigenetic mechanisms regulating gene expression, including DNA methylation, histone modifications controlling chromatin accessibility, and non-coding RNAs. These effects have been suggested to contribute to cancer preventive potential in in vitro and in vivo studies, affecting several key processes such as DNA repair, cell signaling cascades including Wnt-signaling, induction of apoptosis, cell cycle progression, cell proliferation, migration and invasion, epithelial-mesenchymal transition (EMT), metastasis formation and development of drug-resistance. We here summarize the state-of-the-art of IF affecting the epigenome in major hormone-dependent, urogenital, and gastrointestinal tumor types and in in vivo studies on anti-cancer treatment or developmental aspects, and short-term intervention studies in adults. These data, while often requiring replication, suggest that epigenetic gene regulation represents an important novel target of IF and should be taken into consideration when evaluating the cancer preventive potential of IF in humans.

Curcumin Suppresses Proliferation of Colon Cancer Cells by Targeting CDK2

Curcumin, the yellow pigment of turmeric found in Southeast Indian food, is one of the most popular phytochemicals for cancer prevention. Numerous reports have demonstrated modulation of multiple cellular signaling pathways by curcumin and its molecular targets in various cancer cell lines. To identify a new molecular target of curcumin, we used shape screening and reverse docking to screen the Protein Data Bank against curcumin. Cyclin-dependent kinase 2 (CDK2), a major cell-cycle protein, was identified as a potential molecular target of curcumin. Indeed, in vitro and ex vivo kinase assay data revealed a dramatic suppressive effect of curcumin on CDK2 kinase activity. Furthermore, curcumin induced G1 cell-cycle arrest, which is regulated by CDK2 in HCT116 cells. Although the expression levels of CDK2 and its regulatory subunit, cyclin E, were not changed, the phosphorylation of retinoblastoma (Rb), a well-known CDK2 substrate, was reduced by curcumin. Because curcumin induced cell-cycle arrest, we investigated the antiproliferative effect of curcumin on HCT116 colon cancer cells. In this experiment, curcumin suppressed HCT116 cell proliferation effectively. To determine whether CDK2 is a direct target of curcumin, CDK2 expression was knocked down in HCT116 cells. As expected, HCT116 sh-CDK2 cells exhibited G1 arrest and reduced proliferation. Because of the low levels of CDK2 in HCT116 sh-CDK2 cells, the effects of curcumin on G1 arrest and cell proliferation were not substantially relative to HCT116 sh-control cells. From these results, we identified CDK2 as a direct target of curcumin in colon cancer cells.

The P110 subunit of PI3-K is a therapeutic target of acacetin in skin cancer

The identification of primary molecular targets of cancer-preventive phytochemicals is essential for a comprehensive understanding of their mechanism of action. In the present study, we investigated the chemopreventive effects and molecular targets of acacetin, a flavonoid found in Robinia p seudoacacia, also known as black locust. Acacetin treatment significantly suppressed epidermal growth factor (EGF)-induced cell transformation. Immunoblot analysis revealed that acacetin attenuated EGF-induced phosphorylation of Akt and p70(S6K), which are downstream effectors of phosphatidylinositol 3-kinase (PI3-K). An immunoprecipitation kinase assay of PI3-K and pull-down assay results demonstrated that acacetin substantially inhibits PI3-K activity by direct physical binding. Acacetin exhibited stronger inhibitory effects against anchorage-dependent and -independent cell growth in cells expressing higher PI3-K activity compared with those exhibiting relatively low PI3-K activity. Binding assay data combined with computational modeling suggest that acacetin binds in an adenosine triphosphate (ATP)-competitive manner with the p110α subunit of PI3-K and interacts with Val828, Glu826, Asp911, Trp760, Ile777, Ile825, Tyr813, Ile910 and Met900 residues. Acacetin was also found to significantly reduce SK-MEL-28 tumor growth and Akt phosphorylation in vivo. Taken together, these results indicate that acacetin is an ATP-competitive PI3-K inhibitor and a promising agent for melanoma chemoprevention.

Dietary phytochemicals in cancer prevention and therapy: a complementary approach with promising perspectives

The population is aging. Over the coming years, the incidence of age-related chronic diseases such as cancer is expected to continue to increase. Phytochemicals, which are non-nutritive chemicals found in plants and food, have emerged as modulators of key cellular signaling pathways exerting proven anticancer effects. The challenge now is to develop personalized supplements comprised of specific phytochemicals for each clinical situation. This will be possible once a better understanding is gained of the molecular basis explaining the impact of phytochemicals on human health. The aim of the present literature review is to summarize current knowledge of the dietary phytochemicals with proven antitumor activity, with a special emphasis placed on their molecular targets. Also discussed are the limits of existing research strategies and the future directions of this field.

Cruciferous Vegetables: Dietary Phytochemicals for Cancer Prevention

Relationships between diet and health have attracted attention for centuries; but links between diet and cancer have been a focus only in recent decades. The consumption of diet-containing carcinogens, including polycyclic aromatic hydrocarbons and heterocyclic amines is most closely correlated with increasing cancer risk. Epidemiological evidence strongly suggests that consumption of dietary phytochemicals found in vegetables and fruit can decrease cancer incidence. Among the various vegetables, broccoli and other cruciferous species appear most closely associated with reduced cancer risk in organs such as the colorectum, lung, prostate and breast. The protecting effects against cancer risk have been attributed, at least partly, due to their comparatively high amounts of glucosinolates, which differentiate them from other vegetables. Glucosinolates, a class of sulphur- containing glycosides, present at substantial amounts in cruciferous vegetables, and their breakdown products such as the isothiocyanates, are believed to be responsible for their health benefits. However, the underlying mechanisms responsible for the chemopreventive effect of these compounds are likely to be manifold, possibly concerning very complex interactions, and thus difficult to fully understand. Therefore, this article provides a brief overview about the mechanism of such compounds involved in modulation of carcinogen metabolising enzyme systems.