Saucernetin-7 Isolated from Saururus chinensis Induces Caspase-Dependent Apoptosis in Human Promyelocytic Leukemia HL-60 Cells

摘要

In the present study,we investigated the effect of saucernetin-7(a biologically active compound isolated from the underground parts of Saururus chinensi)on the induction of apoptosis and the putative pathways of its action in HL-60 human promyelocytic leukemia cells.Saucernetin-7-treated HL-60 cells displayed several features of apoptosis,including DNA fragmentation,DNA laddering by agarose gel electrophoresis,and externaliza-tion of annexin-V targeted phosphatidylserine(PS)residues.z-VAD-fmk(a broad-caspase inhibitor)almost completely suppressed saucernetin-7-induced DNA ladder formation,thereby implicating the caspase cascade in the apoptotic process.We also observed that saucernetin-7 caused the activations of caspase-3,-8 and-9,and that it induced Bid cleavage,the mitochondrial translocation of Bax from the cytosol,and cytochrome c release from mitochondria,but it had no effect on Bcl-2 and Bcl-xL levels.Taken together,the present study demonstrates that saucernetin-7 is a potent inducer of apoptosis and that its activity is facilitated by caspase-8 activation,Bid cleavage,Bax translocation to mitochondria,release of cytochrome c into cytoplasm,and subsequently caspase-3 activation,which offers a potential mechanism for the apoptosis-inducing activity of saucernetin-7.