Plant‑Derived Agents Targeting Apoptotic Pathways in Non‑Melanoma Skin Cancer: Mechanisms and Nanoformulation Strategies

Non‑melanoma skin cancer (NMSC) remains the most common cutaneous malignancy and continues to rise globally, creating a growing need for safer and more effective therapeutic strategies. Dysregulation of apoptosis represents a central feature of both basal cell carcinoma and cutaneous squamous cell carcinoma, offering a rational target for intervention. Numerous plant‑derived products exhibit selective pro‑apoptotic activity in NMSC models, acting through mitochondrial dysfunction, caspase activation, modulation of BCL‑2 family proteins, and restoration of p53‑linked pathways. However, their clinical translation is limited by poor solubility, instability, and restricted skin penetration. Advances in nanoformulation technologies, including polymeric, lipid‑based, and invasome systems, substantially enhance the delivery, bioavailability, and therapeutic performance of these phytochemicals. This review examines the therapeutic potential of plant‑derived pro‑apoptotic agents and nano‑enabled delivery systems as a forward‑looking direction for next‑generation NMSC management.