Document Detail


Synergistic effects of topoisomerase I inhibitor, SN38, on Fas-mediated apoptosis.
MedLine Citation:
PMID:  21036702     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Anticancer research     Volume:  30     ISSN:  1791-7530     ISO Abbreviation:  Anticancer Res.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-11-01     Completed Date:  2010-12-10     Revised Date:  2011-11-02    
Medline Journal Info:
Nlm Unique ID:  8102988     Medline TA:  Anticancer Res     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  3911-7     Citation Subset:  IM    
Affiliation:
Department of Hematology and Immunology, Kanazawa Medical University, Kahoku-gun, Ishikawa, Japan.
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MeSH Terms
Descriptor/Qualifier:
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:
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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