title: Apoptosis induced by ardipusilloside III through BAD dephosphorylation and cleavage in human glioblastoma U251MG cells.
abstract: 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.
authors.affiliation: Department of Neurosurgery, Xijing Institute of Clinical Neuroscience, Xijing Hospital, Fourth Military Medical University, No127 Changle Western Road, Xi'an 710032, PR China.
authors.forename: Hong
authors.initials: H
authors.lastname: Lin
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhang
authors.forename: Guang
authors.initials: G
authors.lastname: Cheng
authors.forename: Hai-Feng
authors.initials: HF
authors.lastname: Tang
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Hai-Ning
authors.initials: HN
authors.lastname: Zhen
authors.forename: Jin-Xiang
authors.initials: JX
authors.lastname: Cheng
authors.forename: Bo-Lin
authors.initials: BL
authors.lastname: Liu
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Cao
authors.forename: Wen-Peng
authors.initials: WP
authors.lastname: Dong
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
mesh_terms: 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*
chemical_list: C494819:BAD protein, human; D012503:Saponins; C529239:ardipusilloside III; D051025:bcl-Associated Death Protein; D020169:Caspases