| Paclitaxel induces apoptosis via caspase-3 activation in human osteogenic sarcoma cells (U-2 OS). | |
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MedLine Citation:
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PMID: 16140185 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Paclitaxel has been found to exhibit cytotoxic and antitumor activity. There is little information regarding the mechanisms of apoptotic-inducing effect of paclitaxel on human osteogenic sarcoma U-2 OS cells. Several key regulatory proteins are involved in the initiation of apoptosis. Caspase-3 plays a direct role in proteolytic cleavage of cellular proteins responsible for progression to apoptosis. We examined the effect of paclitaxel on the cell cycle arrest and apoptosis in U-2 OS cells using flow cytometric analysis and Western blotting. We also measured the inhibition of paclitaxel-induced apoptosis and the caspase-3 activity by the broad-spectrum caspase inhibitor z-VAD-fmk on U-2 OS cells. The increased levels of casapse-3 were also confirmed by cDNA microarray. Our observations were: (1) paclitaxel treatment resulted in G2/M-cycle arrest in U-2 OS cells; (2) time and dose dependent apoptosis of U-2 OS cells was induced by paclitaxel; (3) in U-2 OS cells, z-VAD-fmk blocked the paclitaxel-induced apoptosis and caspase-3 activation. These results suggest that paclitaxel-induced G2/M-cycle arrest of the G2/M phase and apoptosis via a caspase-3 pathway in U-2 OS cells. |
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Authors:
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K-H Lu; K-H Lue; M-C Chou; J-G Chung |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2005-04-25 |
Journal Detail:
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Title: Journal of orthopaedic research : official publication of the Orthopaedic Research Society Volume: 23 ISSN: 0736-0266 ISO Abbreviation: J. Orthop. Res. Publication Date: 2005 Sep |
Date Detail:
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Created Date: 2005-09-05 Completed Date: 2005-10-27 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8404726 Medline TA: J Orthop Res Country: United States |
Other Details:
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Languages: eng Pagination: 988-94 Citation Subset: IM |
Affiliation:
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Department of Orthopaedic Surgery, Chung Shan Medical University Hospital, Taichung 402, Taiwan, ROC. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Chloromethyl Ketones
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pharmacology Antineoplastic Agents, Phytogenic / pharmacology* Apoptosis / drug effects* Bone Neoplasms / drug therapy*, pathology Caspase 3 Caspases / antagonists & inhibitors, physiology* Cell Cycle / drug effects Cell Line, Tumor Dose-Response Relationship, Drug Enzyme Activation Humans Osteosarcoma / drug therapy*, pathology Paclitaxel / pharmacology* |
| Chemical | |
Reg. No./Substance:
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0/Amino Acid Chloromethyl Ketones; 0/Antineoplastic Agents, Phytogenic; 0/benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; 33069-62-4/Paclitaxel; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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