Dihydroceramide intracellular increase in response to resveratrol treatment mediates autophagy in gastric cancer cells.

Resveratrol has both apoptosis and autophagy-promoting activities in different cancer cells. Dihydroceramide is the immediate precursor of the apoptotic mediator ceramide in the de novo sphingolipid synthesis pathway. Here we demonstrate that resveratrol induces autophagy in HGC-27 cells, with no sign of cell death. Autophagy occurs after an increase in dihydroceramides by inhibition of dihydroceramide desaturase. The effects of resveratrol are mimicked by a dihydroceramide desaturase inhibitor. These results demonstrate that resveratrol-induced autophagy occurs with a rise in intracellular dihydroceramide levels as the result of inhibition of dihydroceramide desaturases activity and that dihydroceramide accumulation is responsible for autophagy promotion.