| Cepharanthin enhances adriamycin sensitivity by synergistically accelerating apoptosis for adriamycin-resistant osteosarcoma cell lines, SaOS2-AR and SaOS2 F-AR. | |
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MedLine Citation:
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PMID: 15201988 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cepharanthin (CEP) is a biscoclaurine alkaloid extracted from Stephania cepharantha Hayata. CEP is reported to inhibit drug resistance by inhibiting P-glycoprotein, a drug efflux pump, and recently to induce apoptosis. In the present study, we examined the effects of CEP as an inhibitor of adriamycin (ADR) resistance on ADR-induced apoptosis and necrosis. First, we established p53-deficient ADR-resistant osteosarcoma cell lines, SaOS2-AR and SaOS2 F-AR. Resistant cells showed a higher level of intracellular glutathione peroxidase activity than parent cells. P-glycoprotein was overexpressed in resistant cells. The intracellular ADR level of resistant cells was lower than that of parent cells. One micro g/ml CEP eliminated the degradation of intracellular ADR of resistant cells; that is, to a level equivalent to that of the parent cells. CEP of 0.5 micro g/ml, which was not cytotoxic when used alone, significantly increased the ADR sensitivity of resistant cells, to a level similar to the parent cell level. Isosorbide 5-mononitrate, a potential nitric oxide-generation agent, combined with CEP further increased the ADR sensitivity of resistant cells, indicating a synergistic effect of CEP and isosorbide 5-mononitrate on ADR cytotoxicity. Time-lapse microscopic observation revealed that ADR dominantly induced apoptosis much more than necrosis for both parent and resistant cells, and that the use of 0.5 micro g/ml CEP with ADR synergistically accelerated apoptosis in resistant cells. Finally, we clarified the property by which CEP synergistically accelerates ADR-induced apoptosis. This property might be a new mechanism that explains how CEP overcomes ADR resistance. |
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Authors:
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Kuniaki Katsui; Masahiro Kuroda; Yadi Wang; Megumi Komatsu; Kengo Himei; Mitsuhiro Takemoto; Shiro Akaki; Jun-Ichi Asaumi; Susumu Kanazawa; Yoshio Hiraki |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: International journal of oncology Volume: 25 ISSN: 1019-6439 ISO Abbreviation: Int. J. Oncol. Publication Date: 2004 Jul |
Date Detail:
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Created Date: 2004-06-17 Completed Date: 2005-04-25 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 9306042 Medline TA: Int J Oncol Country: Greece |
Other Details:
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Languages: eng Pagination: 47-56 Citation Subset: IM |
Affiliation:
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Department of Radiology, Okayama University Medical School, Okayama 700-8558, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Alkaloids
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pharmacology* Antineoplastic Agents, Phytogenic / pharmacology* Apoptosis / drug effects* Benzylisoquinolines Biological Transport Bone Neoplasms Cell Line, Tumor Doxorubicin / pharmacokinetics, toxicity* Drug Resistance, Neoplasm* Drug Synergism Humans Osteosarcoma |
| Chemical | |
Reg. No./Substance:
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0/Alkaloids; 0/Antineoplastic Agents, Phytogenic; 0/Benzylisoquinolines; 23214-92-8/Doxorubicin; 481-49-2/cepharanthine |
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