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.