Dioscin induced activation of p38 MAPK and JNK via mitochondrial pathway in HL-60 cell line.

Saponins have shown promise in cancer prevention and therapy; however, little is known about the detailed signaling pathways underlying their anticancer activities. In the present study, we examined the mechanisms of action of dioscin, a glucosides saponin isolated from Polygonatum zanlanscianense pump, in human myeloblast leukemia HL-60 cells. Dioscin suppressed HL-60 cell growth in a dose-dependent manner. This inhibition was due to the induction of apoptosis as revealed by the externalization of phosphatidylserine, and cleavages of lamin A/C and PARP-1. Treatment with dioscin induced apoptosis through activation of caspases 3, 7, 8, 9, and 10. Phosphorylation of p38 MAPK and JNK contributed to dioscin-induced apoptosis upstream of caspase activation. Using various inhibitors and antioxidant agents, we found that mitochondrial derived reactive oxygen species and depletion of mitochondrial transmembrane potential lead to the phosphorylation of p38 MAPK and JNK. Taken together, our results demonstrated that dioscin induces apoptosis by activation of p38 MAPK and JNK through the caspase-dependent mitochondrial death pathway. This work suggests that dioscin may be used as a drug lead for the treatment of myeloblast leukemia.