Euphol from Euphorbia tirucalli induces human gastric cancer death through the degradation of TGFβR in lipid raft membrane microdomain (657.12)

Abstract

Transforming growth factor‐β (TGF‐β) is correlated with poorer prognosis in gastric cancer. Therefore, inhibition of the TGF‐β pathway is an attractive strategy for the treatment of cancer. In this study, we demonstrated that euphol, a euphane‐type triterpene alcohol, attenuated TGF‐β‐induced smad2 phosphorylation, and induced gastric cancer cell death through mitochondrial‐dependent apoptosis. Euphol enriched TGF‐β receptors expression in cell membrane lipid raft microdomain within an hour, and promoted them degradation within 24 hours. The interaction of lipid membrane and euphol was confirmed by liquid chromatography‐mass spectrometry and Biacore‐surface plasmon resonance analysis. In conclusion, our results suggest that euphol may distribute membrane protein TGF‐β receptors in lipid rafts, and these membrane modifications may induce cancer cell death.Grant Funding Source: Supported by Grant from the Department of Health, Executive Yuan, ROC (DOH100‐TD‐C‐111‐002)