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.
Signorelli
Paola
P
Laboratory of Biochemistry and Molecular Biology, San Paolo University Hospital, Medical School, University of Milan, Italy.
Munoz-Olaya
Jose M
JM
Gagliostro
Vincenzo
V
Casas
Josefina
J
Ghidoni
Riccardo
R
Fabriàs
Gemma
G
D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D002518:Ceramides / Q000032:analysis / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D010088:Oxidoreductases / Q000037:antagonists & inhibitors; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013440:Sulfides / Q000494:pharmacology
D002518:Ceramides; D013267:Stilbenes; D013440:Sulfides; C530382:XM 462; C109343:dihydroceramide; D010088:Oxidoreductases; C108138:dihydroceramide desaturase; D000077185:Resveratrol