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The Journal of nutritional biochemistry

Gamma-tocotrienol profoundly alters sphingolipids in cancer cells by inhibition of dihydroceramide desaturase and possibly activation of sphingolipid hydrolysis during prolonged treatment.


PMID 28456081

Abstract

Vitamin E gamma-tocotrienol (γTE) is known to have anticancer effects, but mechanisms underlying these actions are not clear. Here using liquid chromatography tandem mass spectrometry, we show that γTE induced marked changes of sphingolipids including rapid elevation of dihydrosphingosine and dihydroceramides (dhCers) in various types of cancer cells. The elevation of dihydrosphingolipids coincided with increased cellular stress, as indicated by JNK phosphorylation, and was prior to any sign of induction of apoptosis. Chemically blocking de novo synthesis of sphingolipids partially counteracted γTE-induced apoptosis and autophagy. Experiments using