Resveratrol inhibits the phosphatidylinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway in the human chronic myeloid leukemia K562 cell line

Resveratrol inhibits the initiation, promotion and progression of tumors, however, the mechanism by which resveratrol inhibits the proliferation of the human chronic myeloid leukemia K562 cell line remains unclear. The present study was conducted to investigate the effect of resveratrol on the activation of the phosphatidylinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling cascade in K562 cells. Resveratrol showed significant cytotoxic effects and induced apoptosis in K562 cells in a dose- and time-dependent manner. In addition, resveratrol attenuated the phosphorylation of PI3K, Akt and mTOR in the K562 cells. Furthermore, the selected inhibitors of PI3K (LY294002), Akt (SH-6) and mTOR (rapamycin) enhanced the effects of resveratrol in K562 cells. In addition, cyclin D1 levels were found to decrease and the activation of caspase-3 was observed. Resveratrol was also found to significantly attenuate the phosphorylation of the downstream molecules, p70S6K and 4EBP1. These results suggested that the downregulation of the PI3K/Akt/mTOR signaling cascades may be a crucial mediator in the inhibition of proliferation and induction of apoptosis by resveratrol in K562 cells.