Apoptosis induced by ardipusilloside III through BAD dephosphorylation and cleavage in human glioblastoma U251MG cells.
Ardipusilloside III is a saponin newly isolated from Ardisia pusilla A.DC. Since saponins have exhibited broad anti-cancer and pro-apoptotic activity, we investigated the ability of ardipusilloside III to induce apoptosis in human glioblastoma U251MG cells, as well as the involvement of apoptotic signaling pathways. Ardipusilloside III markedly suppressed proliferation of U251MG cells in a time- and dose-dependent manner (P < 0.05, IC50 = 8.2 microg/ml), but did not affect the growth of primary cultures of human astrocytes. Ardipusilloside III-treated U251MG cells underwent typical apoptotic changes. Exposure to a low dose of ardipusilloside III provoked G2/M-phase cell cycle arrest, which preceded apoptosis characterized by the appearance of cells with sub-G1 DNA content. However, a higher dose of ardipusilloside III induced apoptosis without first causing cell cycle arrest. In addition, ardipusilloside III exposure resulted in time-dependent BAD dephosphorylation and cleavage as well as activation of caspase-8 and caspase-3. Therefore, both the intrinsic pathway of apoptosis, mediated by BAD dephosphorylation and cleavage, and the extrinisic pathway of apoptosis, mediated by caspase-8 and caspase-3 activation, were involved in ardipusilloside III-induced apoptosis. These data suggest that ardipusilloside III is a reliable candidate for chemotherapeutic treatment of human glioblastomas, and should be investigated further.
Lin
Hong
H
Department of Neurosurgery, Xijing Institute of Clinical Neuroscience, Xijing Hospital, Fourth Military Medical University, No127 Changle Western Road, Xi'an 710032, PR China.
Zhang
Xiang
X
Cheng
Guang
G
Tang
Hai-Feng
HF
Zhang
Wei
W
Zhen
Hai-Ning
HN
Cheng
Jin-Xiang
JX
Liu
Bo-Lin
BL
Cao
Wei-Dong
WD
Dong
Wen-Peng
WP
Wang
Peng
P
D017209:Apoptosis / Q000187:drug effects*; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D020169:Caspases / Q000378:metabolism*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D053837:DNA Cleavage; D005909:Glioblastoma; D006801:Humans; D046529:Microscopy, Electron, Transmission; D012503:Saponins / Q000494:pharmacology*; D051025:bcl-Associated Death Protein / Q000378:metabolism*
C494819:BAD protein, human; D012503:Saponins; C529239:ardipusilloside III; D051025:bcl-Associated Death Protein; D020169:Caspases