title: Dioscin induced activation of p38 MAPK and JNK via mitochondrial pathway in HL-60 cell line.
abstract: 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.
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Macao SAR, China. Electronic address: emilyywang@umac.mo.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes and Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou, China.
authors.forename: Qing-Yu
authors.initials: QY
authors.lastname: He
authors.affiliation: Open Laboratory for Tumor Molecular Biology, Department of Biochemistry, Shantou University Medical College, Shantou, China; Department of Anatomy, The University of Hong Kong, Hong Kong SAR, China. Electronic address: jfchiu@hkucc.hku.hk.
authors.forename: Jen-Fu
authors.initials: JF
authors.lastname: Chiu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004144:Diosgenin / Q000031:analogs & derivatives* / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; C019357:dioscin; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020169:Caspases; D004144:Diosgenin
keywords: Apoptosis; Dioscin; MAPK; Mitochondria; Reactive oxygen species; Saponin