Jaceosidin induces apoptosis through Bax activation and down-regulation of Mcl-1 and c-FLIP expression in human renal carcinoma Caki cells

Abstract

Jaceosidin is a flavonoid isolated from Artemisia vestita that has been reported to possess anti-tumor and anti-proliferative activities in many cancer cells. In this study, we investigated the anti-tumor activity of jaceosodin in renal carcinoma cells. Jaceosidin induced apoptosis in multiple human renal carcinoma cells (Caki, ACHN, A498, and 786-O), lung cancer cells (A549) and glioma cells (U251MG). In contrast, jaceosidin does not induce apoptosis in normal human umbilical vein cells (EA.hy926). Apoptotic cell death was associated with the activation of caspase-3 and cleavage of poly (ADP-ribose) polymerase. Treatment with jaceosidin also caused loss of mitochondrial membrane potential (MMP) and Bax activation, which led to the release of cytochrome c into the cytosol. We also found that jaceosidin downregulated Mcl-1 and c-FLIP expression at the transcriptional level and that ectopic expression of Mcl-1 and c-FLIP blocked jaceosidin-induced apoptosis. Cumulatively, our results suggest that jaceosidin induces apoptosis in renal carcinoma cells through Bax activation and reduces Mcl-1 and c-FLIP expression.

Keywords: Apoptosis; Bax; Jaceosidin; Mcl-1; Renal cancer; c-FLIP.