1109 Resveratrol-berberine combination significantly inhibits melanoma cells growth

Melanoma is among the most life-threatening cancers. Despite recent therapeutic advances, management of melanoma remains difficult. Therefore, new mechanism-based approaches are needed. Our previous study found that SIRT6 can inhibited the primary melanoma growth through an autophagy-dependent manner. It was indicated the potential of SIRT6 to be a therapeutic target in melanoma. Resveratrol, sirtuins classical agonist, has been shown to afford chemopreventive and therapeutic effects against melanoma. A number of in vitro and in vivo studies have suggested potential usefulness of resveratrol in melanoma management. However, its rapid metabolism limited the clinical use, which indicated that it is necessary to combine with other agents to postpone its metabolism. Berberine, has been shown to inhibit melanoma cell growth. Interestingly, resveratrol and berberine, both are found in several herbal medicine and plants, indicating their natural association. In this study, we tested the hypothesis that resveratrol-berberine combination may have better efficacy against melanoma than either of the individual use, in addition to its own effect, can enhance the bioavailability of each other, thereby imparting superior anti-proliferative efficacy. We found that resveratrol-berberine combination resulted in a superior anti-proliferative response in human melanoma cell lines (WM35 and WM793B) as assessed by CCK8 assay for cell growth and viability. Further, the flow cytometry analysis revealed significant cell cycle arrest in the G1 phase in the same cell lines. However, the combination promoted the apoptosis of melanoma cells. Our data demonstrated that resveratrol-berberine combination was markedly superior to either of the individual agents, in intervention setting when treatment was started. Further studies are ongoing in our laboratory to verify the in vitro data and determine the mechanisms associated with the observed effect of resveratrol-berberine combination.