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 sig­
nificant role in combating drug resistance. The review underscores the importance of understanding the mo­
lecular 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.