Dietary polyphenols in colorectal cancer – Mechanisms, clinical evidence, and bioavailability of curcumin, resveratrol, and epigallocatechin-3-gallate: A review

Dietary polyphenols have attracted considerable interest as potential preventive and therapeutic agents in colorectal cancer (CRC), although their clinical value remains uncertain. This narrative review aimed to critically evaluate the mechanistic, epidemiological, and clinical evidence for curcumin, resveratrol, and epigallocatechin-3-gallate (EGCG), with particular emphasis on the gap between preclinical activity and human efficacy. PubMed/MEDLINE, Scopus, and Web of Science were searched for English-language studies published from January 2000 to January 2026, including in vitro and animal investigations, epidemiological studies, and clinical trials. Preclinical evidence consistently showed that these polyphenols inhibit nuclear factor kappa B (NF-κB), phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin (PI3K/Akt/mTOR), signal transducer and activator of transcription 3 (STAT3), and Wnt/β-catenin signaling, while promoting apoptosis, antioxidant responses, and suppression of inflammation, proliferation, angiogenesis, and metastasis. These effects were associated with reduced tumor burden in animal models. Epidemiological studies suggested modest protective associations, particularly for green tea consumption, but findings were inconsistent, frequently confounded, and of limited generalizability. Human trials predominantly demonstrated biomarker modulation, whereas effects on adenoma recurrence were mixed and no consistent benefits were observed for tumor regression, recurrence, progression-free survival, or overall survival. Clinical translation is further limited by poor absorption, rapid metabolism, uncertain activity of metabolites, formulation variability, and potential hepatotoxicity and drug interactions, although high local colorectal exposure may remain biologically relevant. Curcumin, resveratrol, and EGCG therefore show strong mechanistic potential but cannot currently be recommended as stand-alone CRC therapies. They should be regarded as investigational preventive or adjunctive agents pending adequately powered randomized trials using standardized formulations, optimized dosing, and clinically meaningful endpoints.