Introduction

NCDs are long-term disease conditions that develop gradually due to genetic, physiological, environmental, lifestyle, and dietary factors. The most prevalent NCDs globally include diabetes, cancer, chronic respiratory diseases, and cardiovascular disorders. The incidence rate of NCDs is increasing globally and nationally. ¹ Cancer, marked by uncontrolled cell proliferation and potential metastasis, is a major global health threat. ² Every day, cancer is detected in 52,900 people, causing more than 27,000 deaths. Projections suggest that by 2040, the global burden of cancer will reach 28 million new cases and 16.2 million deaths annually.³ Conventional cancer treatments like surgery, chemotherapy, and radiotherapy often come with significant adverse effects. However, recent advancements in oncology have introduced innovative approaches such as ablation therapy, catalytic cancer therapy, iron-dependent cell death therapy, gene modification therapy, nanoparticle-based therapy, radionics, stem cell therapy, sonodynamic therapy, and targeted therapy. While these advanced therapies offer promising alternatives for cancer treatment, their high costs create significant barriers to accessibility, making them unaffordable for individuals from various socio-economic backgrounds. ⁴

Findings from medical and nutrition research indicate that dietary agents enhance anticancer activity and regulate several physiological functions. In the field of cancer research and therapy, scientists are currently exploring numerous chemical components produced from plants that can effectively fight and prevent cancer. ⁵ Phytochemicals/phytoconstituents/ non-nutritive compounds present in herbs, leaves, vegetables, fruits and other plant sources have attracted considerable attention because of their prospective roles in cancer inhibition and therapy due to the complexity of their structures, their unique biological effects, affordability, ease of use, and comparatively fewer harmful side effects. ^6,7 The anticarcinogenic properties of these non-nutritive compounds include modulation of molecular signaling pathways, inhibition of early-stage carcinogenesis, protein modifications, and interaction with specific molecular signals. ⁸

Good nutrition is vital for maintaining metabolic homeostasis. Inclusion of specific foods and beverages in the diet can alter metabolic pathways by enhancing or diminishing them. Diets mainly comprised of plants include a broad variety of consumption habits marked by reduced animal-derived goods and a predominance of plant-based foods abundant in various phytochemical groups. ⁹ Herbs, spices, legumes, whole grains, vegetables, fruits, oilseeds, and nuts provide essential micronutrients, including vitamins, minerals, enzymes, and phytochemicals, all contributing to cellular protection and cancer prevention. Epidemiological and mechanistic studies suggest that adherence to a plant-based diet that is well balanced, with limited consumption of red meat and meats that are processed meats, is linked with a lower incidence of breast, prostate, colorectal, and lung cancers. ^{10, 11} Regarding diet patterns for the prevention of cancer, prioritizing suitable plant-centred food selections is essential. This review systematically compiles and evaluates the phytochemicals and bioactive compounds present in various plant-based food groups, delineating their molecular mechanisms of cancer prevention as evidenced in preclinical models and human clinical studies.

Materials and Methods

This review compiles and analyzes the current scientific evidence on the anticancer potential of phytochemicals, emphasizing their molecular mechanisms and translational relevance from preclinical models to clinical applications. A literature survey was performed in various research databases such as Google Scholar, PubMed, Scopus, and Web of Science, to identify pertinent peer-reviewed publications. The search included original research articles and review papers published between 2018 and 2025. The following keywords and Boolean operators were used to refine the search:

(“phytochemicals” OR “plant-derived compounds”) AND (“anticancer activity” OR “cancer therapy”)

(“natural compounds” AND “molecular mechanisms” AND “cancer”)

(“preclinical studies” OR “in vitro” OR “in vivo“) AND (“phytochemicals” AND “oncogenic pathways”)

(“clinical trials” AND “phytochemicals” AND “cancer treatment”)

The manuscripts for this review article were chosen upon fulfilling certain eligibility and exclusion criteria.

Inclusion criteria

Studies investigating the anticancer effects of phytochemicals with mechanistic insights.

Research papers detailing apoptotic pathways, autophagy modulation, angiogenesis inhibition, cell cycle regulation, or interactions with other oncogenic pathways.

Preclinical studies (both in vitro and in vivo) and clinical trials evaluating phytochemical-based cancer therapies.

Peer-reviewed publications in English with clearly defined methodologies and experimental outcomes.

Exclusion criteria

Studies lacking mechanistic insights or focusing solely on general phytochemical properties without cancer-specific findings.

Non-peer-reviewed sources, conference abstracts, and unpublished reports. 

Phytochemicals as targeted cancer therapeutic agents

In recent years, growing scientific evidence has highlighted the powerful role of phytochemicals in reducing cancer risk. Phytochemicals present in plant-based foods exert protective effects against cancer through multiple molecular mechanisms. Naturally occurring compounds, including flavonoids, phytosterols, phenolic acids, carotenoids, and stilbenes, help combat cancer by inducing apoptosis, inhibiting angiogenesis, and modulating inflammatory and oxidative stress pathways. ¹²

Flavonoids

Flavonoids are natural compounds in plants, consisting of 2 rings of benzene connected by 3 carbon atoms, creating a C6-C3-C6 structure. They are classified into subclasses, including chalcones, dihydrochalcones, flavones, and flavanols, based on the oxidation level of the central chain and the B-ring attachment. ¹³ Common dietary sources of flavonoids include EGCG (cocoa and green tea), hesperidin and hesperetin (citrus fruits), quercetin in (apples, berries, broccoli, grapes, red onions, and red wine), luteolin (carrots, celery, chili peppers, lettuce, and spinach), and apigenin (artichokes, chamomile, oregano, and parsley). ¹⁴ Flavonoids reduce tumor progression through apoptosis and cell-cycle regulation. Flavonoids cause G2/M phase arrest and promote cell death in breast cancer cells by altering two pathways (p53 and PTEN). ¹⁵ EGCG regulates the 67-KDa laminin receptor, influences JAK/STAT, MAPK, and PI3K/AKT signaling pathways, and affects estrogen and androgen receptors in breast and prostate tumors, respectively. ¹⁶ Quercetin induces DNA damage, decreases BCL2 levels, and activates caspase-3 to trigger apoptosis. It sensitizes prostate cancer cells to paclitaxel by modulating proteins like GRP78 and hnRNPA1. ¹⁷ Apigenin’s anti-angiogenic properties are associated with cell cycle cessation, apoptosis induction, and regulation of signaling pathways. ¹⁸

Phytosterols

Phytosterols are plant-derived compounds resembling cholesterol, differing mainly by an extra hydrocarbon chain at the C-24 site. Over 250 phytosterols have been identified, with campesterol, β-sitosterol, stigmasterol, β-sitostanol, and campestanol being the most common in food sources. ¹⁹ These compounds show anticancer properties by enhancing pro-apoptotic signals that cause cell death by increasing calcium concentration in the cytosol and mitochondrial region. Phytosterols promote the overexpression of unfolded protein response signals and endoplasmic reticulum-mitochondria axis signals, leading to endoplasmic reticulum stress and cancer cell death. They also decrease the production of ROS, facilitating cell death via intrinsic mitochondrial apoptotic pathways or extrinsic death receptor pathways. Phytosterols hinder cell cycle progression by suppressing PCNA expression and disrupting the MAPK pathway, while also reducing cell migration and aggregation. ²⁰ They help the immune system identify and kill cancer-causing cells. ²¹ β-sitosterol inhibits the propagation of human colon cancer cells by obstructing the LEF-1-mediated Wnt/β-catenin pathway. The increased expression of LEF-1 in intestinal cancer triggers this pathway, causing the growth of tumors. ²² β-Sitosterol impedes the advancement and invasiveness of HCT116 CC cells by lowering LEF-1 levels, disrupting the pathway, and diminishing key downstream targets, including Survivin and CCND1, supporting its effectiveness as a cancer-fighting agent.

Phenolic acids

The cancer-fighting ability of phenolic acids comes from their antioxidant effects. They act as free radical scavengers and metal binding agents, strengthen the body’s antioxidant defense mechanisms, and regulate key proteins and transcription factors (NRF2). ^{23, 24} Their role involves blocking cell growth via the ERK1/2 pathway, D-type cyclins, and CDK, alongside hindering angiogenesis by targeting VEGF and MIC-1, suppressing oncogenic signaling (PI3K/AKT), inducing apoptosis, and inhibiting cellular migration and metastasis. Their ability to fight against cancer is amplified through epigenetic influencers and resistance regulators, effectively reducing cancer cell division, inhibiting metastasis, and promoting cell death. ²⁵ Phenolic acids, such as caffeic, dihydro cinnamic, and p-coumaric acids extracted from propolis, along with EGCG extracted from green tea, act as epigenetic agents for TNBC. ²⁶ Administration of coumaric acid and EGCG led to a marked decline in cell viability across four TNBC cell lines (BT-20, BT-549, MDA-MB-231, and MDA-MB-436). Molecular docking predicted that these compounds bind to the MTAse territory of human DNMT1, competing with its endogenous inhibitor SAH. While EEP did not modify overall DNA methylation, EEP and EGCG were found to cause demethylation of the RASSF1A gene in BT-549 cells. EEP treatment also influenced RASSF1 protein expression, highlighting propolis as a potential agent for epigenetic therapies aimed at DNA methylation modulation. Chlorogenic acids present in tea help mitigate disease risk by regulating signaling pathways involved in inflammation and oxidative damage, regulating essential key cellular functions such as proliferation, apoptosis, and immune responses. By interacting with specific molecular mechanisms, chlorogenic acids suppress tumor growth. Research studies of phenolic acids in ovarian cancer have identified promising anticancer effects. GA suppresses tumor development via the PTEN/AKT/HIF-1α pathway. Salicylic acid regulates multiple pathways, including Wnt/β-catenin, and targets ovarian cancer stem cells. EA prevents angiogenesis and cisplatin resistance, facilitating apoptosis. PCA reduces cancer cell growth by inducing apoptosis and regulating oxidative stress. CA enhances cisplatin cytotoxicity, while coumaric acid and ferulic acid act as adjuvants, modulating oxidative stress and signaling pathways. ²⁷

Stilbenes

Dietary stilbenes are polyphenolic compounds found in many plants, such as berries, grapes, and medicinal herbs. Certain examples of notable stilbenes are compounds such as resveratrol (trans-3,4′,5-trihydroxystilbene), abundant in grapes and red wine are known for their oxidative stress reducing, immune regulating, and cancer fighting effects. Pterostilbene (trans-3,5-dimethoxy-4′-hydroxystilbene), a more bioavailable counterpart of resveratrol found in blueberries and grapes, exhibits enhanced pharmacokinetics. Piceatannol (trans-3,5,3′,4′-tetrahydroxystilbene), present in red wine and passion fruit, functions as a tyrosine kinase inhibitor with anticancer potential. Other derivatives, such as piceid (resveratrol glucoside), astringin (piceatannol glucuronide), ε-viniferin, pallidol (resveratrol dimers), and gnetin C (a resveratrol dimer found in melinjo seeds), demonstrate anti-angiogenic and chemopreventive effects. These stilbenes control epigenetic pathways, specifically methylation of DNA, alteration of histone, and regulation of microRNA, contributing to their therapeutic efficacy, causing programmed cell death, lowering angiogenesis, and inflammatory responses. ^{28, 29} Methoxy-stilbenes exhibit anticancer activity by modulating key receptors and enzymes linked with the biosynthesis of estrogen in breast cancer cells. ³⁰ Finings indicated that methoxy-stilbenes efficiently suppressed the action of two key enzymes involved in estrogen synthesis (aromatase and 17HSD17β). They are also involved in suppressing the expression of Erα, thereby weakening estrogen signalling and preventing cancer cell proliferation. Whole grape extracts may have more therapeutic benefits than isolated stilbenes. MBE, a rich source of resveratrol, piceatannol, and pterostilbene, showed greater potency than resveratrol by stimulating apoptosis and enforcing cell cycle arrest. ³¹   Resveratrol combats photo-carcinogenesis by adjusting apoptotic inhibition proteins and governing cell cycle signalling cascades. Stilbenes prevent prostate cancer through inhibition of MTA1 signaling pathways. Resveratrol and pterostilbene suppressed MTA1 expression, leading to reduced tumor growth, metastasis, and angiogenesis while enhancing apoptosis. ³²

Carotenoids

Carotenoids are lipophilic pigments classified into carotenes and xanthophylls, which contribute to the red, yellow, and orange colours in fruits and vegetables. Beyond their roles as antioxidants, anti-inflammatories, and provitamin A sources, carotenoids demonstrate significant anticancer activity through mechanisms such as free radical neutralization, gene regulation, and modulation of inflammatory pathways. Key dietary sources of carotenoids include algae, yeast, carrots, tomatoes, citrus fruits, and various plant by-products. ³³ Saponified lipophilic extract from sea buckthorn (Hippophae rhamnoides L.) has anticancer effects against breast cancer cell lines T47D and BT-549. ³⁴ The extract inhibited proliferation (IC₅₀ value: 16 µM), reduced ROS levels, and induced apoptosis (80.29% in T47D and 40.6% in BT-549). Carotenoids derived from yeast through cost-effective fermentation processes, demonstrating dose-dependent cytotoxicity against MCF7 and MDA-MB-231 cells (IC₅₀ values: 29.11 and 7.82 μg/mL) while sparing normal HEK293T cells. ³⁵ Similarly, carotenoids derived from Paracoccus sp. EGY7, identifying zeaxanthin (48.3%) as the predominant compound. The extract exhibited cytotoxicity against MDA-MB-231 cells (IC₅₀ value: 1200 µg), inhibited cellular migration, and induced apoptosis through modulation of BAX/BCL2 ratios. ³⁶ α-Carotene suppresses metastasis by modulating MMP2, MMP2, TIMP-1, and PAI-1, thereby impairing integrin β1/FAK/MAPK signaling without affecting primary tumor growth. β-Carotene inhibits gastric cancer progression through Notch/EMT pathway suppression, and in neuroblastoma, it downregulates MMPs, HIF-1α, and VEGF, consequently reducing metastasis. Additionally, it modulates M2 macrophage and fibroblast activation, limiting invasiveness in colorectal cancer. Overexpression of β-carotene 15,15′-oxygenase suppresses neuroblastoma self-renewal and metastasis through regulation of EMT and MMPs. ³⁷

Major mechanistic anti-cancer potential of phytochemicals

Anti-angiogenesis and metastasis

Angiogenesis is the process by which old blood vessels are converted into new ones, crucial for tumor growth, invasion, and dissemination. Phenolic compounds serve as angiogenesis blockers to inhibit the multiplication of tumor cells.  Polyphenol compounds such as EGCG, ellagic acid, and genistein counteract angiogenesis by inhibiting VEGF, PDGF, HIF-1α, and MMPs. Inhibition of platelet-derived growth factor (PDGF) receptor phosphorylation and epidermal growth factor receptor also aids in anti-angiogenesis. ³⁸ Green tea polyphenols chelate ferrous ions and stop the proliferation of cancer cells driven by HIF 1α. In vitro studies on prostate tumor cells showed that EGCG treatment reduced HIF 1α-mediated transcription and protein levels under normal oxygen conditions. ³⁹ Galanin, kaempferol, myricetin, and quercetin inhibit the tubular development of HUVECs mediated by vascular endothelial growth factor and impede U937 cell adherence to HUVECs. ⁴⁰ Flavonoids, including kaempferol, genistein, apigenin, rutin, and naringin, reduce the levels of vascular endothelial growth factor in cells of human breast cancer. ¹⁴ Metastasis is the process by which cancer cells travel through lymph nodes to distant organs, interchangeable with angiogenesis, invasion, cell adhesion, migration, proteolysis, and extracellular matrix destruction. ⁴¹ Many dietary polyphenolic compounds disrupt tumor cell adhesion and migration, giving them anti-invasive and antimetastatic properties, though their precise signaling pathways and molecular mechanisms remain unidentified. ⁴² Curcumin inhibits VEGF/VEGFR2 signalling and downstream pathways (AKT, MAPK), reducing endothelial cell proliferation and migration. It also suppresses MMP2/9 expression and EMT by modulating Wnt/β-catenin pathways. ⁴³ Resveratrol downregulates cyclin D1/CDK4 and VEGF expression, blocking endothelial cell activation, while Quercetin hinders CAM assay angiogenesis by targeting VEGF and HIF-1α. ⁴⁴ Apigenin blocks STAT3 nuclear translocation, impairing endothelial tubulogenesis, while Genistein induces apoptosis in VEGF-loaded endothelial cells by inhibiting JNK/p38 and MMP-2/9. Luteolin downregulates PURB-mediated MAPK/PI3K pathways, reducing NSCLC angiogenesis. ⁴⁵  

Cell Cycle Arrest and Apoptosis

Apoptosis, a prevalent form of regulated cell death, is a critical target for various cancer therapies. Dietary cancer-fighting agents such as apigenin, chrysin, curcumin, EGCG, ellagic acid, resveratrol, and silymarin suppress carcinogenesis through the induction of apoptosis. ⁴⁶ Notably, cancer cells exhibit heightened sensitivity to these agents compared to normal healthy cells. In sarcoma cells, EGCG induces apoptosis through mechanisms including cell cycle cessation at the G2/M phase, suppression of BCL-2, and the activation of p53 and BAX. ⁴⁷ In prostate cancer cells, apoptosis is accompanied by the overexpression of BAX, along with the activation of caspases (3 and 8). EGCG primarily triggers and promotes senescence and apoptosis through p53-mediated signaling, in conjunction with the role of BAX. ⁴⁸ Theaflavin, a phenolic compound in black tea, contributes to apoptosis by enhancing DNA fragmentation, activating caspases (3 and 8), increasing and decreasing the levels of BCL-2. ⁴⁹ Furthermore, theaflavin activates the expression of caspases 9 and 3 in prostate cancer cells, alters the BAX/BCL-2 ratio, increases the release of cytochrome c from mitochondria, and causes apoptosis via p53 expression. ⁵⁰ Anthocyanins, a significant class of flavonoids, demonstrated dose-related suppression of the growth of colon cancer cells. They induce programmed cell death in colon cancer cells through DNA damage and an imbalance in BAX and BCL-2 expression. However, certain bioflavonoids, including epicatechin, rutin, chlorogenic acid, and p-hydroxybenzoic acid, do not exhibit growth-inhibiting effects. ⁵¹ Delphinidin, a naturally occurring anthocyanidin, obstructs VEGF-induced cell movement and growth by arresting the cell cycle at the G0/G1 phase. The levels of Cyclin D1 and cyclin A significantly decreased. ⁵² Additionally, early activation of extracellular signal-regulated protein kinase 1/2, overexpression of caveolin-1, and downregulation of Ras contribute to the antiproliferative effects of delphinidin. ⁵³

Modulation of cell signalling pathways

Phytochemicals exhibit various biological activities like anti-inflammatory, antiproliferative, antioxidant, antimutagenic, and immunomodulatory, which help regulate cancer progression and influence cancer development by modulating multiple signaling pathways. ⁵⁴ They modulate routes concerned with cancer progression and suppression, such as the PI3K/Akt/mTOR/P70S6K pathway, PPARs, Nrf2, JAK-STAT, HIF-1, TGF-β, and TLR/NLRP, as well as the MAPK, ERK, and p38 pathways.  ^55-57 Phytochemicals can scavenge free radicals and respond to chemical stress, activating or inhibiting diverse signaling responses. Notable phytochemicals like apigenin, betulinic acid, ascorbic acid, curcumin, resveratrol, lycopene, and sesamol have protective effects through these pathways. ⁵⁸ Resveratrol decreases the capacity of colorectal cancer cells to develop and metastasize. The mechanism indicates a connection between the modulation of the peroxisome proliferator gamma receptor coactivator 1-alpha signaling pathway and AMP-activated protein kinase. ⁵⁹ Resveratrol suppresses ERK1/2 phosphorylation, limits gene expression associated with tumor progression. Resveratrol and curcumin act on Ras mutations that cause continuous activation of the MEK/ERK/MEK/Raf/Ras pathway, driving cell growth and survival. ⁶⁰ Flavonoids such as luteolin, apigenin, and kaempferol inhibit AKT/mTOR/P13K signalling pathway, essential for cell survival, growth, and metastasis, while promoting apoptosis by suppressing AKT phosphorylation and modulating downstream regulators (STAT3). ⁶¹ Another dietary flavonoid, Fisetin, in combination with 5-FU treatment reduced PI3K expression, AKT activation, mTOR, its downstream targets, and mTOR signaling complex in PIK3CA-mutant cells. ⁶² Table 1 provides an overview of the regulatory pathways modulated by phytochemicals and their impact on cancer metabolism.

Table 1: Regulatory Pathways Modulated by Phytochemicals in Cancer Metabolism

Figure 1: Anticancer mechanism of phytochemicals: Pathways and molecular targets Click here to view Figure

In 2020, GLOBOCAN reported 19.3 million new cases of cancer worldwide, ranking India third behind the US and China. Projections indicate that by 2040, the percentage of people suffering from cancer in India will rise to 2.08 million, reflecting a 57.5% increase from 2020. ^{76, 77} Cancer can develop in nearly any organ or system within the human body, including the oral cavity, breast, bone, brain, stomach, intestines, lungs, renal organs, genitals, and the reproductive system. According to a recent review, the five most common cancer locations across various anatomical sites in Indian men include the stomach (4.8%), prostate (6.1%), tongue (5.9%), mouth (8.4%), and lung (10.6%). For women, the most commonly reported cancer sites were breast (28.8%), cervix (10.6%), ovary (6.2%), corpus uteri (3.7%), and lung (3.7%). Furthermore, based on estimated incidence rates, cumulative risk, and total cancer burden across all anatomical sites, the most prevalent cancers were those of the digestive system (1 in 39 individuals), breast (1 in 56), genital system (1 in 53), oral cavity (1 in 62), and respiratory system (1 in 74). Among digestive system cancers, the most frequently diagnosed malignancies included the stomach (1 in 213), liver (1 in 276), and colorectal cancer (1 in 295). In contrast, lung cancer remained the predominant malignancy in the respiratory system (1 in 101). 78 The anticancer potential of phytochemicals derived from various food sources is supported by animal and human studies. Tables 2-6 present their correlation with a reduced incidence of conditions such as breast, lung, colon, stomach, liver, and prostate cancer, along with the underlying mechanisms of their anticancer activity. These tables also highlight the effectiveness of phytochemicals in cancer prevention and mitigation.

Table 2: Anticancer effects of phytochemicals in various animal models

Table 3: Cancer protective properties of whole grains

Table 4: Association between red and processed meat consumption and cancer risk

 Table 5: Cancer protective mechanisms of fruits and vegetables

 Table 6: Cancer protective potential of nuts, oilseeds, and tea

 Challenges in the bioavailability of phytochemicals

Phytochemicals provide a wide range of health benefits, but their full therapeutic potential is often affected by factors such as limited bioavailability and stability. After oral ingestion, several processes, including digestion, absorption, metabolism, distribution, and excretion, affect the bioavailability of phytochemicals.¹¹³ The structural and compositional characteristics of food matrices are crucial in determining how phytochemicals are released during digestion. These compounds are entrapped within the cell walls and influence their bioaccessibility. Food processing techniques, particularly thermal treatments, cause the release of these functional compounds by disrupting their natural cell structure. ¹¹⁴ These processing techniques also result in degradation of thermolabile compounds due to oxidative and hydrolytic reactions. The natural physical and chemical properties, such as crystallinity and fat solubility, determine the absorption and bioavailability. The chemical traits, such as hydrophobicity, molecular weight, can impede their solubility and transport across the gastrointestinal epithelium. Physiological factors such as changes in gastrointestinal pH, enzymatic functions, and the presence of specific transport systems also impact their absorption rate. Antinutritional factors, including phytates, tannins, and oxalates, interact with phytochemicals and form complexes, thus diminishing their bioavailability. Dietary fibers hinder the absorption of fat-soluble compounds by modifying their interaction with lipid micelles. ¹¹⁵ After the process of absorption, metabolism either enhances or decreases their bioactivity of phytochemicals. This metabolic process is influenced by gut microbiota, which can affect their chemical structures and biological functions. ¹¹⁶

Table 7 presents an overview of phytochemical bioavailability, highlighting its challenges, underlying mechanisms, and strategies for enhancement.

Table 7: Phytochemical Bioavailability: Challenges, Mechanisms, and Enhancement Strategies

Discussion

Cancer remains one of the most challenging NCDs to treat due to its complex pathophysiology, heterogeneity, and ability to develop resistance to conventional therapies. Chemotherapy is associated with severe side effects, including systemic toxicity and damage to non-cancerous cells. In this context, incorporating naturally derived bioactive compounds into cancer treatment regimens has emerged as a highly promising strategy. The integration of phytochemicals with conventional chemotherapeutic agents has garnered significant attention in recent years.

This review provides an in-depth over view of the role of specific phytochemicals, particularly flavonoids, phenolic acids, phytosterols, stilbenes, and carotenoids in preventing and treating cancer. These non-nutritive compounds found in whole grains, fruits, vegetables, and leaf extracts exhibit antioxidant, anti-inflammatory, and anticancer effects.  Their anticarcinogenic effects are mainly mediated through the modulation of critical intracellular signaling pathways involved in cancer pathophysiology. Key signaling cascades influenced by these non-nutritive compounds include the PI3K/Akt/mTOR pathway, which controls cell growth, survival, and metabolism; the NF-κB signaling pathway, central to inflammation and immune response; and the MAPK/ERK pathway, which controls cell proliferation and differentiation. Furthermore, they play an essential role in regulating and maintaining the autophagy-apoptosis balance. Phytochemicals exert a multi-targeted mode of action by interacting with various molecular targets simultaneously, in contrast to conventional chemotherapeutic agents, which exhibit single pathway specificity while destroying cancer cells. The potential of phytochemicals to simultaneously disrupt several signalling cascades improves cancer treatment.

Extensive preclinical studies using in vitro and in vivo models have demonstrated the anticancer effects of these phytochemicals across a range of cancer types, including breast, colon, prostate, lung, and liver cancers. Moreover, clinical trials and meta-analyses of cohort and prospective studies have provided epidemiological evidence supporting the protective role of diets rich in different phytochemicals. These findings highlight the potential of plant-based diets as adjuncts or alternatives to conventional cancer therapies, emphasizing the significance of dietary interventions in cancer prevention and therapy.

Conclusion

Cancer continues to pose a significant global health burden, necessitating the development of cost-effective, safe, and widely accessible therapeutic strategies. Increasing attention is being directed toward natural products due to their easy accessibility and affordability. Among these natural compounds, phytochemicals have emerged as promising compounds for anticancer drug development. This review offers a comprehensive examination of key phytochemicals, particularly flavonoids, phenolic acids, stilbenes, phytosterols, and carotenoids as anticancer agents. The underlying mechanisms of action, including modulation of critical signaling pathways, apoptosis induction, anti-inflammatory effects, and antioxidative activity, are discussed in detail, supported by evidence from both preclinical studies and human clinical trials.

Clinical trials remain the gold standard for evaluating therapeutic efficacy and safety. While meta-analyses of cohort and prospective studies have highlighted the potential anticancer effects of dietary phytochemicals against various cancer types, several limitations persist. These include variability in the phytochemical content of foods, influenced by factors such as plant variety, cultivation conditions, processing methods, and challenges related to bioavailability. The latter is particularly critical, as the absorption, metabolism, and systemic availability of phytochemicals can significantly impact their biological efficacy.

Although numerous experimental studies have explored strategies to enhance phytochemical bioavailability, such as nano formulations, co-administration with bioenhancers, and structural modifications, clinical research on the pharmacokinetics, potential nutrient interactions, optimal dosing, and long-term safety of isolated or enriched phytochemicals remains limited. Further well-designed human studies are essential to translate promising laboratory findings into effective, evidence-based interventions for cancer prevention and therapy.

Acknowledgement

The authors acknowledge the institutional support (M.O.P. Vaishnav College for Women, Autonomous), Chennai, for providing access to scientific databases and academic resources that helped in the compilation of information.

Funding Sources

The author(s) received no financial support for the research, authorship, and/or publication of this article

Conflict of Interest

The authors do not have any conflicts of interest.

Data Availability Statement

Although adequate data have been presented in tables and figures, all authors affirm that any additional data will be provided upon request if needed.

Ethics Statement

This research did not involve human participants, animal subjects, or any material that requires ethical approval.

Informed Consent Statement

This study did not involve human participants, and therefore, informed consent was not required.

Permission to Reproduce Material from Other Sources

Not applicable

Clinical Trial Registration

This research does not involve any clinical trials. 

Author Contributions

• Sarah Jane Monica: Conceived the idea, drafted the manuscript, supervised, reviewed, edited, and enhanced the overall quality of the manuscript
• Deevena Jemima: Conceived the idea, prepared tables, and contributed to drafting the manuscript.
• Esther Lydia D: Created figures, supervised, and contributed to drafting the manuscript.
• Priyadarshini S: Prepared tables and contributed to drafting the manuscript.
• Anne Mary Preetha: Prepared tables and contributed to drafting the manuscript.
• Emi Grace Mary Gowshika Rajendran: Contributed to drafting the manuscript.

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List of Abbreviations

17HSD 17β: 17β-hydroxysteroid dehydrogenases

ATA: Antcin – A

BAX: BCL2 Associated X

BCL-2: B cell lymphoma 2

BT – 20: Breast cancer cell line – 20

BT – 549: Breast cancer cell line – 549

cagA: Cytotoxin–associated gene A

CAMP: Campesterol

CAT: Catalase

CCND1: Cyclin D1

CCS: Case-control studies

CDK: Cyclin-dependent kinases

CFL2:  Cofilin-2

COX: Cyclooxygenase

CS: Cohort study

DMH: Dimethylhydrazine

DNMT1: DNA methyltransferase 1

EEP: Ethanolic extract of propolis

EGCG: Epigallocatechin gallate

EMT: Epithelial-mesenchymal transition

ERGO: Ergosterol

ERK: Extracellular signal-regulated kinase

FADD: Fas-associated protein with death domain

FOXO: Forkhead box transcription factors

G2/M: Second gap phase/Mitosis

GPX: Glutathione peroxidase

GRP78: Glucose-regulated protein 78

HCA: Heterocyclic amines

HEK293T: Human embryonic kidney 293 cells

HER2: Human epidermal growth factor receptor 2

HIF 1α: Hypoxia–inducible factor 1 alpha

hnRNPA1: Heterogeneous nuclear ribonuclear protein

H. pylori: Helicobacter pylori

HUVEC: Human umbilical vein endothelial cells

IL-6: Interleukin

JAK/STAT: Janus kinases/Signal transducer and activator of transcription

LEF -1: Lymphoid enhancer factor

MAPK: Mitogen–activated protein kinase

MBE: Muscadine grape berry extract

MCF7: Michigan Cancer Foundation 7

MDA – MB – 231: MD Anderson – metastatic breast 231

MDA – MB – 436: MD Anderson – metastatic breast 436

MEK: Mitogen–activated extracellular signal-regulated kinase

MIC 1: Macrophage inhibitory cytokine – 1

MMP: Matrix metalloproteinase

MTA 1: Metastasis-associated protein 1

MTase: Methyltransferase

mTOR: Mammalian target of rapamycin

NCD: Non-communicable diseases

NFR2: Nuclear factor erythroid 2-related factor 2

NLRP: Nucleotide-binding and leucine-rich repeat protein

NSCLC: Non-small cell lung cancer

OR: Odds ratio

P13K/AKT: phosphatidylinositol 3 kinase/Akt kinase

p53: Tumour protein

PAI-1: Plasminogen activator inhibitor-1

PAH: Polycyclic aromatic hydrocarbons

PCNA: Proliferating cell nuclear antigen

PG: Prostaglandin

PIK3CA: Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha

PPARS: Peroxisome proliferator-activated receptors

PTEN: Phosphatase and tensin homolog

Raf: Rapidly accelerated fibrosarcoma

Ras: Rat sarcoma

RASSFIA gene: Ras association domain family member 1

ROS: Reactive oxygen species

RR: Relative risk

SITO: Sitosterol

SOD: Superoxide dismutase

STAT3: Signal transducer and activator of transcription 3

STIG: Stigmasterol

TGF-β: Transforming growth factor β

TIMP: Tissue inhibitors of metalloproteinases

TLR: Toll-like receptors

TNBC: Triple negative breast cancer

TNF–α: Tumor necrosis factor-alpha

TRAIL: Tumor Necrosis Factor (TNF)-related apoptosis-inducing ligand

VEGF: Vascular endothelial growth factor