EMERGING ANTITUMOR MECHANISMS OF PLANT SECONDARY METABOLITES: BEYOND CLASSICAL CYTOTOXICITY

Plant secondary metabolites have historically been invaluable sources of anticancer drugs, with compounds such as paclitaxel, vincristine, and camptothecin serving as mainstays of chemotherapy. Classical anticancer mechanisms have focused on direct cytotoxicity through microtubule disruption, topoisomerase inhibition, and DNA intercalation. However, emerging research has revealed that plant secondary metabolites exert pleiotropic anticancer effects through diverse mechanisms beyond classical cytotoxicity. This review critically examines emerging antitumor mechanisms of plant secondary metabolites, including the regulation of apoptosis, metastasis inhibition, autophagy modulation, reversal of multidrug resistance, targeting of cancer stem cells, epigenetic modulation, and immunomodulatory effects. We synthesize current understanding of the molecular pathways targeted by plant-derived compounds, including the PI3K/AKT/mTOR pathway, MAPK/ERK signaling, and the NF-κB inflammatory cascade. Case studies of selected compounds, including curcumin, resveratrol, and epigallocatechin gallate, illustrate the diversity of anticancer mechanisms. Despite significant advances, challenges including poor bioavailability and the need for predictive biomarkers persist. This review identifies promising research directions and discusses the potential for combination therapies targeting multiple pathways.