| Synergistic effects of topoisomerase I inhibitor, SN38, on Fas-mediated apoptosis. | |
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MedLine Citation:
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PMID: 21036702 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Inhibitors of topoisomerase I, such as camptothecin, have proven to be among the most promising new classes of anti-neoplastic agents introduced into the clinical setting in recent years. Irinotecan (CPT-11) is one of the most widely used camptothecin analogs and is converted to form the active metabolite SN-38. The present study was designed to explore apoptosis induced by SN38 and anti-Fas antibody (CH11) in WR/Fas-SMS1 cells and its possible mechanisms. The results demonstrate that combination of SN38 and CH11 synergistically enhanced cell apoptosis in WR/Fas-SMS1 cells. Western blotting analysis showed that combination of SN38 and CH11 activated the ATM-Chk1-p53 pathway, increased protein expression of phospho-p53 and cleavaged caspase-3, but down-regulated expression of phospho-p21. Our data suggest that combination of SN38 and CH11 enhanced apoptosis through down-regulation of p21 phosphorylation. In conclusion, inhibition of p21 could be a new adjuvant approach in cancer therapy. |
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Authors:
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Yan Cao; Zhe-Xiong Jin; Xiao-Peng Tong; Sun Yue; Tomoyuki Sakai; Takafumi Kawanami; Toshioki Sawaki; Miyuki Miki; Haruka Iwao; Akio Nakajima; Yasufumi Masaki; Yoshihiko Fukushima; Yoshimasa Fujita; Hideo Nakajima; Toshiro Okazaki; Hisanori Umehara |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Anticancer research Volume: 30 ISSN: 1791-7530 ISO Abbreviation: Anticancer Res. Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-11-01 Completed Date: 2010-12-10 Revised Date: 2011-11-02 |
Medline Journal Info:
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Nlm Unique ID: 8102988 Medline TA: Anticancer Res Country: Greece |
Other Details:
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Languages: eng Pagination: 3911-7 Citation Subset: IM |
Affiliation:
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Department of Hematology and Immunology, Kanazawa Medical University, Kahoku-gun, Ishikawa, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antibodies, Monoclonal / pharmacology* Antigens, CD95 / genetics, immunology* Apoptosis / drug effects Camptothecin / analogs & derivatives*, pharmacology Caspase 3 / metabolism Cell Cycle Proteins / metabolism Cell Line, Tumor DNA-Binding Proteins / metabolism Drug Synergism Enzyme Activation / drug effects Humans Lymphoma, T-Cell / drug therapy, enzymology, immunology, pathology Mice Protein Kinases / metabolism Protein-Serine-Threonine Kinases / metabolism Topoisomerase I Inhibitors / pharmacology* Tumor Suppressor Protein p53 / metabolism Tumor Suppressor Proteins / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Antibodies, Monoclonal; 0/Antigens, CD95; 0/Cell Cycle Proteins; 0/DNA-Binding Proteins; 0/Topoisomerase I Inhibitors; 0/Tumor Suppressor Protein p53; 0/Tumor Suppressor Proteins; 100286-90-6/irinotecan; 7689-03-4/Camptothecin; EC 2.7.-/Protein Kinases; EC 2.7.11.1/Checkpoint kinase 1; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/ataxia telangiectasia mutated protein; EC 3.4.22.-/Caspase 3 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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