Proteomic approach to study the cytotoxicity of dioscin (saponin).
Dioscin, extracted from the root of Polygonatum zanlanscianense pamp, exhibits cytotoxicity towards human myeloblast leukemia HL-60 cells. Proteomic analysis revealed that the expression of mitochondrial associated proteins was substantially altered in HL-60 cells corresponding to the dioscin treatment, suggesting that mitochondria are the major cellular target of dioscin. Mitochondrial functional studies validated that mitochondrial apoptotic pathway was initiated by dioscin treatment. Changes in proteome other than mitochondrial related proteins implicate that other mechanisms were also involved in dioscin-induced apoptosis in HL-60 cells, including the activity impairment in protein synthesis, alterations of phosphatases in cell signaling, and deregulation of oxidative stress and cell proliferation. Current study of protein alterations in dioscin-treated HL-60 cells suggested that dioscin exerts cytotoxicity through multiple apoptosis-inducing pathways.
Wang
Ying
Y
Department of Chemistry and Open Laboratory of Chemical Biology, University of Hong Kong, Pokfulam, Hong Kong, PR China.
Cheung
Yim Hing
YH
Yang
Zhiqi
Z
Chiu
Jen-Fu
JF
Che
Chi-Ming
CM
He
Qing-Yu
QY
D017209:Apoptosis; D004144:Diosgenin / Q000031:analogs & derivatives* / Q000633:toxicity; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D015180:Electrophoresis, Gel, Two-Dimensional; D018922:HL-60 Cells; D006801:Humans; D008564:Membrane Potentials; D008928:Mitochondria / Q000187:drug effects; D008956:Models, Chemical; D031384:Polygonatum; D040901:Proteomics / Q000379:methods*; D012503:Saponins / Q000633:toxicity*; D016622:Silver Staining; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D012503:Saponins; C019357:dioscin; D004144:Diosgenin