Cancer remains one of the leading causes of mortality worldwide, mainly due to its capacity to evade apoptosis, a tightly regulated process essential for maintaining cellular homeostasis. The dysregulation of apoptotic pathways, involving key molecular regulators such as caspases, Bcl-2 family proteins, and inhibitor of apoptosis proteins (IAPs), contributes to cancer progression and therapeutic resistance. This review provides a comprehensive overview of apoptosis's intrinsic (mitochondrial) and extrinsic (death receptor-mediated) pathways, distinguishing them from necrotic cell death and highlighting their roles in tumour suppression. Amid growing interest in alternative and adjunctive therapies, medicinal plants have emerged as a rich source of bioactive compounds capable of selectively modulating apoptosis in cancer cells. We explore the therapeutic potential of phytochemicals, including alkaloids, flavonoids, terpenoids, and phenolics that exhibit pro-apoptotic activity across diverse cancer models. Special attention is given to the synergistic effects of plant-derived compounds in crude extracts and their combinatorial use with conventional chemotherapeutics, which may enhance efficacy and reduce toxicity. By integrating mechanistic insights with preclinical findings, this review underscores the strategic promise of plant-based agents in modern oncology. Incorporating natural products into cancer therapy represents a novel and rational therapeutic approach. We also address challenges such as compound standardization, bioavailability, and mechanistic validation, while proposing future directions for research to unlock the full potential of phytotherapy in precision cancer medicine.
Kasumbwe et al. (Tue,) studied this question.