Polyphenol-Rich Formulations and Their Multi-Target Interactions With Molecular Pathways in Cancer Cells

Abstract

Cancer remains the second leading cause of death globally, with classical therapies limited by selectivity, toxicity, and resistance. This review examines polyphenol-rich preparations and their multi-target interactions in cancer cells. Polyphenols (flavonoids, phenolic acids, stilbenes, lignans) simultaneously modulate multiple targets, addressing key cancer hallmarks: sustained proliferative signaling, apoptosis evasion, replicative immortality, and angiogenesis. Key pathways include PI3K/Akt/mTOR, MAPK, RAS, and p53. Notable compounds like curcumin, resveratrol, quercetin, and EGCG induce apoptosis, inhibit angiogenesis, arrest cell cycle, and modulate epigenetics. Despite encouraging preclinical evidence, clinical translation faces challenges from low bioavailability, rapid metabolism, and conflicting data. Strategies include stable derivatives, nano-encapsulation, personalized medicine, and combination with established drugs. Polyphenolic compounds emerge as promising multi-target anticancer agents with low toxicity. Further research on bioavailability and trials is needed.