Resveratrol suppresses melanoma growth by promoting autophagy through inhibiting the PI3K/AKT/mTOR signaling pathway

Resveratrol (RV) is a natural polyphenolic phytoalexin derived from peanuts, red grape skins and red wine, and has been demonstrated to alleviate multiple types of malignancies. However, how RV achieves this in melanoma is unknown. The aim of present study was to investigate the role of RV in melanoma, using Cell Counting Kit-8, flow cytometry and western blot analysis. RV inhibited melanoma cell viability, migration and invasion counteracting melanoma progression. In addition, proteins associated with autophagy, including Beclin 1 and microtubule-associated protein 1A/1B-light chain 3 (LC3)-II/I, were upregulated, whereas p62 expression was downregulated in RV-treated cells. The number of LC3(+) puncta, which can be applied to represent autophagosome formation, increased following RV treatment, suggesting that RV may trigger autophagy in melanoma cells. Treatment with the autophagy inhibitor, 3-methyladenine, reversed the RV-dependent inhibition of viability, migration and invasion of melanoma cells. RV treatment also reduced the ratios of phosphorylated (p)-AKT/AKT and p-mTOR/mTOR in melanoma cells. In conclusion, these findings suggested that RV may inhibit the viability and migration of melanoma cells through inhibiting the AKT/mTOR pathway, thus triggering autophagy. This indicated that RV may serve as an innovative therapeutic for melanoma treatment.