Resveratrol synergistically enhances anti-lung cancer efficacy with myricetin and dihydromyricetin on A549 cells by increasing their intracellular concentrations

The present study aimed to investigate the synergistic cytotoxic effects and related mechanism of resveratrol and myricetin or dihydromyricetin in A549 cells. Cell viability, scratch wound, clone formation, cell apoptosis and cycle test were operated to confirm the synergistic anti-lung cancer effects. The effects of resveratrol on the efflux of myricetin, dihydromyricetin and rhodamine 123 were determined to discover the synergistic mechanism. The combination of resveratrol of 25 µg/mL and myricetin or dihydromyricetin of 25 µg/mL had the best synergistic anti-lung cancer effect. Resveratrol combined with myricetin or dihydromyricetin caused A549 cells to exit the S- and G2/M-phase. Resveratrol enhanced the myricetin, dihydromyricetin and rhodamine 123 concentrations in A549 cells. Resveratrol and myricetin or dihydromyricetin exert a synergistic effect, but not <i>via</i> a suppression of P-glycoprotein.