Induction of p27kip1 by 2,4,3′,5′- tetramethoxystilbeneis regulated by protein phosphatase 2A-dependent Akt dephosphorylation in PC-3 prostate cancer cells

Abstract

trans-Stilbenes induce cytochrome P450 1B1 (CYP1B1) inhibition and cell death. 2,4,3′,5′tetramethoxystilbene (TMS), a synthetic trans-stilbene analog, induced apoptotic cell death in PC-3 prostate cancer cells, as evidenced by a decrease in the mitochondrial membrane potential. TMS-induced apoptosis was associated with an increase in the level of cell cycle inhibitor, p27kip1, through reduction of Akt-mediated Skp2 expression. TMS-induced activation of protein phosphatase 2A (PP2A) inhibited Akt phosphorylation and p27kip1 expression, indicating that PP2A is involved in the induction of p27kip1 via Akt inhibition. These results suggest that TMS may inhibit the cell cycle through induction of p27kip1, leading to apoptotic cell death in PC-3 prostate cancer cells.