Effects of resveratrol on the expression of PTEN, AKT and MAP kinases; and the effects of PI3K/AKT and MAPK pathways on resveratrol-induced apoptosis.

<p>(A), PANC-1 cells were treated with or without resveratrol (0–20 µM) for 24 h. The cells were harvested and the expression of PTEN, phospho-AKT, AKT, Ras, phospho-ERK, ERK, phospho-JNK, JNK, phospho-p38 and p38 was measured by Western blotting. (B), AKT kinase activity. PANC-1 cells were treated with resveratrol (0–20 µM) for 24 h. AKT kinase activity was measured as we described in materials and methods. Data represent the mean ± S.D. *, #, %, and @ = significantly different from respective controls, P<0.05. (C), PTEN and dominant negative AKT enhance resveratrol-induced apoptosis. PANC-1 and AsPC-1 cells were transiently transfected with empty vector (pcDNA3.1), PTEN wild type (PTEN-WT) or dominant negative AKT (AKT-DN) along with pCMV-LacZ vector (as transfection control) for 24 h. After medium replacement, cells were treated with resveratrol (10 µM) for 48 h and, apoptosis was measured by TUNEL assay. Data represent the mean ± S.D. * and # = significantly different from respective controls, P<0.05. (D), PANC-1 and AsPC-1 cells were pretreated with AKT inhibitor IV (1 µM) and/or MEK1/2 inhibitor PD98059 (10 µM) for 2 h, followed by treatment with or without resveratrol (10 µM) for 48 h. At the end of incubation period, cells were harvested and apoptosis was measured by TUNEL assay. Data represent mean ± SD. *, ** and # = significantly different from respective controls, P<0.05.