Mechanistic insights into plant-derived natural compounds for the treatment of skin cancer: Targeting molecular signaling for therapeutic intervention.

Skin cancer, a prevalent global cancer, is primarily caused by chronic environmental exposures and cellular signaling pathway deregulation. Traditional therapies like radiation, chemotherapy, and surgery face toxicity, resistance, and recurrence issues. Natural compounds, with their diverse biological activity and minimal side effects, are increasingly recognized as potential therapeutic agents. This review explores the potential of natural compounds in treating skin cancer by modifying key molecular signaling pathways, including MAPK/ERK, PI3K/Akt, NF-κB, STAT3, and Wnt/β-catenin. Curcumin, resveratrol, quercetin, epigallocatechin gallate, and genistein are natural substances known to have potent anticancer effects by inhibiting cell proliferation, promoting apoptosis, and preventing metastasis. These substances regulate inflammation, prevent angiogenesis, enhance drug effectiveness, combat multidrug resistance, and have low toxicity to healthy skin cells, indicating potential therapeutic use. Additionally, their compatibility with current chemotherapeutic drugs underscores their significant role in combating drug resistance. The review underscores the importance of understanding the molecular mechanisms underlying phytochemicals' anticancer properties to facilitate their integration into modern treatment methods. Future initiatives should focus on clinical validation, increasing bioavailability, and targeting administration schemes to maximize the therapeutic potential of natural chemicals against skin cancer.