Polyphenols Target Apoptosis and Cell Cycle Regulation in Various Cancer Models: Emphasis on Flavonoid Subclasses

Cancer remains a major global health concern, driving the ongoing search for safer and more effective therapeutic agents. Naturally occurring polyphenolic compounds, including flavonoids, have gained considerable attention for their diverse pharmacological activities, particularly their ability to modulate cancer cell proliferation and apoptosis. This review summarizes current evidence on the anticancer potential of polyphenols and their subclasses across various human cancer cell lines, emphasizing their mechanisms in inducing programmed cell death and regulating cell cycle progression. Key flavonoids such as apigenin, quercetin, and kaempferol, along with other polyphenols like resveratrol and curcumin, exhibit significant anticancer effects through the activation of intrinsic and extrinsic apoptotic pathways and modulation of key cell cycle checkpoints. In vitro studies consistently demonstrate dose dependent cytotoxicity, mitochondrial membrane disruption, caspase activation, and regulation of p53, Bcl-2, cyclins, and CDKs in breast, colon, lung, prostate, and cervical cancer models. Despite encouraging preclinical outcomes, limitations such as poor bioavailability, inter-model variability, and lack of standardized protocols persist. Furthermore, synergistic interactions with conventional chemotherapeutics and advancements in delivery systems and molecular profiling tools may enhance their clinical relevance. Overall, polyphenols, particularly flavonoids, represent a promising class of anticancer agents warranting further translational and clinical exploration.