Document Detail

A novel DNA topoisomerase I inhibitor with different mechanism from camptothecin induces G2/M phase cell cycle arrest to K562 cells.
MedLine Citation:
PMID:  21033700     Owner:  NLM     Status:  MEDLINE    
DNA topoisomerase I (Top1) is an essential nuclear enzyme and a validated target for anticancer agent screening. In a previous study, we found that indolizinoquinoline-5,12-dione derivatives show significant biological activity against several human cancer cell lines. To understand their mechanism of inhibition of cancer cell growth, one indolizinoquinoline-5,12-dione derivative, CY13II, was further studied as lead. Our present results indicate that CY13II shows more potent antiproliferative activity against K562 cells than camptothecin. Additionally, K562 cells were arrested in G2/M, and their growth rate decreased after treatment with CY13II at micromolar concentration. Biochemical Top1 assays indicate that CY13II exhibits a different inhibitory mechanism from camptothecin. Unlike camptothecin, CY13II specifically inhibits the catalytic cleavage activity of Top1 instead of forming the drug-enzyme-DNA covalent ternary complex.
Ning Wu; Xi-Wei Wu; Keli Agama; Yves Pommier; Jun Du; Ding Li; Lian-Quan Gu; Zhi-Shu Huang; Lin-Kun An
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't     Date:  2010-11-08
Journal Detail:
Title:  Biochemistry     Volume:  49     ISSN:  1520-4995     ISO Abbreviation:  Biochemistry     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-24     Completed Date:  2010-12-30     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  0370623     Medline TA:  Biochemistry     Country:  United States    
Other Details:
Languages:  eng     Pagination:  10131-6     Citation Subset:  IM    
Institute of Medicinal Chemistry, Sun Yat-sen University, Guangzhou 510006, China.
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MeSH Terms
Camptothecin / pharmacology
Cell Division / drug effects
Cell Proliferation / drug effects
DNA Topoisomerases, Type I / metabolism*
Indolizines / pharmacology*
K562 Cells
Quinolones / pharmacology*
Topoisomerase I Inhibitors / pharmacology*
Grant Support
Z01 BC006161-24/BC/NCI NIH HHS
Reg. No./Substance:
0/Indolizines; 0/Quinolones; 0/Topoisomerase I Inhibitors; 0/ethyl 7-fluoro-5,12-dioxo-5,12-dihydroindolizino(2,3-g)quinoline-6-carboxylate; 7689-03-4/Camptothecin; EC Topoisomerases, Type I

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