Resveratrol downregulates PI3K/Akt/mTOR signaling pathways in human U251 glioma cells
Hao Jiang, Xia Shang, Hongtao Wu, Subhash C. Gautam, Shaza Al-Holou, Christina Li, Jarret Kuo, Lijie Zhang and Michael Chopp
Resveratrol (trans-3, 4’, 5-trihydroxystilbene) is a naturally occurring polyphenolic compound that has antiinflammatory, antioxidant, neuroprotective properties and acts as a chemopreventive agent. Resveratrol causes cell cycle arrest and induces apoptotic cell death in various types of cancer cells. In the current studies, the effect of resveratrol on phosphoinositide kinase-3 (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway was examined in human U251 glioma cells. Resveratrol decreased both the expression and phosphorylation of Akt. Inhibitors of PI3K (LY294002) and Akt (SH-6) enhanced resveratrolinduced LDH release and caspase-3 activation. Resveratrol reduced phosphorylation of ribosomal protein S6 and the mTOR inhibitor rapamycin further enhanced resveratrol-induced cell death. These results suggest that the downregulation of PI3K/Akt/mTOR signaling pathways may be an important mediator in resveratrol-induced apoptosis in glioma cells.
Keywords: resveratrol; glioma; Akt; caspases-3