Induction of apoptosis of the human leukemia cells by arctigenin and its mechanism of action

This study investigated the effect of arctigenin (ARG) on the induction of apoptosis and the putative pathways of its action in HL-60 and K562 cells. MTT assay was used to detect the cytotoxic effect of ARG in HL-60 and K562 cells. The apoptosis was observed by Hoechst 33258 fluorescence staining and DNA agarose gel electrophoresis. Caspase-3 enzyme activity was measured by caspase-3 enzyme activity detection kit. The expression of related protein was analyzed by Western blotting and the vascular endothelial growth factor (VEGF) level was determined by enzyme-linked immunosorbent assay (ELISA). ARG-treated HL-60 cells and K562 cells exhibited growth inhibition and displayed several features of apoptosis, including DNA fragmentation and DNA laddering by agarose gel electrophoresis. It was observed that poly-(ADP-ribose) polymeras (PARP) were cleaved to smaller molecules and ARG induced upregulation of bax and downregulation of bcl-2 protein expression. However, it had no effect on VEGF levels. Taken together, this study demonstrated that ARG is a potent inducer of apoptosis and this was accompanied by caspase-3 activation and upregulation of bax/bcl-2, which offers a potential mechanism for the apoptosis-inducing activity of ARG.