Comparative proteomic analysis of indioside D-triggered cell death in HeLa cells.
Medicinal plants represent a rich source of cancer drug leads. Indioside D, a furostanol glycoside isolated from Solanum mammosum, was found to possess antiproliferative activity toward a panel of human cancer cell lines. Proteomic analysis of indioside D-treated HeLa cells revealed profound protein changes related to energy production and oxidative stress, suggesting that mitochondria dysfunction plays a role in indioside D-induced apoptosis. Indioside D caused a rapid dissipation of mitochondrial transmembrane potential (DeltaPsim) and the generation of reactive oxygen species (ROS), leading to the activation of caspase-dependent apoptotic cell death. The Fas death receptor pathway was also activated following indioside D treatment, and triggered the activation of caspase-8 and cleavage of Bid, which also acted through the mitochondrial apoptosis pathway. These results suggest that indioside D induced apoptosis in HeLa cells via both intrinsic and extrinsic cell death pathways.
Wong
Chi Chun
CC
School of Biological Sciences, Department of Anatomy, The University of Hong Kong, Hong Kong SAR, China.
Wang
Ying
Y
Cheng
Ka-Wing
KW
Chiu
Jen-Fu
JF
He
Qing-Yu
QY
Chen
Feng
F
D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D006027:Glycosides / Q000737:chemistry / Q000494:pharmacology*; D006367:HeLa Cells / Q000187:drug effects*; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D015394:Molecular Structure; D020543:Proteome / Q000032:analysis / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D053218:Receptors, Death Domain / Q000378:metabolism; D013256:Steroids / Q000737:chemistry / Q000494:pharmacology*
D006027:Glycosides; D020543:Proteome; D017382:Reactive Oxygen Species; D053218:Receptors, Death Domain; D013256:Steroids; C428264:indioside D; D020169:Caspases