| Apoptosis induced by ardipusilloside III through BAD dephosphorylation and cleavage in human glioblastoma U251MG cells. | |
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MedLine Citation:
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PMID: 18181022 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Hong Lin; Xiang Zhang; Guang Cheng; Hai-Feng Tang; Wei Zhang; Hai-Ning Zhen; Jin-Xiang Cheng; Bo-Lin Liu; Wei-Dong Cao; Wen-Peng Dong; Peng Wang |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Apoptosis : an international journal on programmed cell death Volume: 13 ISSN: 1360-8185 ISO Abbreviation: Apoptosis Publication Date: 2008 Feb |
Date Detail:
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Created Date: 2008-01-30 Completed Date: 2008-06-03 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9712129 Medline TA: Apoptosis Country: United States |
Other Details:
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Languages: eng Pagination: 247-57 Citation Subset: IM |
Affiliation:
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Department of Neurosurgery, Xijing Institute of Clinical Neuroscience, Xijing Hospital, Fourth Military Medical University, No127 Changle Western Road, Xi'an 710032, PR China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis
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drug effects* Astrocytes / cytology, drug effects*, metabolism, ultrastructure Caspases / metabolism* Cell Cycle Cell Line, Tumor DNA Cleavage Glioblastoma Humans Microscopy, Electron, Transmission Saponins / pharmacology* bcl-Associated Death Protein / metabolism* |
| Chemical | |
Reg. No./Substance:
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0/BAD protein, human; 0/Saponins; 0/ardipusilloside III; 0/bcl-Associated Death Protein; EC 3.4.22.-/Caspases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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