Dioscin (saponin)-induced generation of reactive oxygen species through mitochondria dysfunction: a proteomic-based study.
It is generally believed that traditional Chinese medicine such as saponins has great value as potent cancer prevention and chemotherapeutic agents; however, the molecular basis for their activities is for the most part lacking. In the present study, we used proteomics to examine the cytotoxic effect of dioscin, a glucoside saponin, on human myeloblast leukemia HL-60 cells. Dioscin induced apoptosis in HL-60 cells in a time-dependent manner. Protein profiling of the microsomal fraction with enriched plasma membrane proteins isolated from HL-60 cells revealed that proteins act as chaperones and/or mediators of protein folding and were substantially altered in expression cells upon dioscin stimuli. Further biochemical study indicated that mitochondria dysfunction caused generation of reactive oxygen species (ROS), leading to the changes in protein expression. The mitochondrial transmembrane potential (DeltaPsi m) inhibitor aristolochic acid (ArA) partially abrogated the dioscin-initiated death receptor apoptosis pathway and cell death. The current study provided detailed evidence to support that dioscin is capable of inducing apoptosis in mammalian cells, in which the mitochondria-initiated apoptosis pathway plays an important role.
Wang
Ying
Y
Department of Chemistry, The University of Hong Kong, Hong Kong SAR, People's Republic of China.
Che
Chi-Ming
CM
Chiu
Jen-Fu
JF
He
Qing-Yu
QY
D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D004144:Diosgenin / Q000031:analogs & derivatives* / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D008969:Molecular Sequence Data; D040901:Proteomics; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012503:Saponins / Q000494:pharmacology*
D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D012503:Saponins; C019357:dioscin; D004144:Diosgenin