Document Detail


Analysis of inhibition of topoisomerase IIalpha and cancer cell proliferation by ingenolEZ.
MedLine Citation:
PMID:  20175785     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We previously reported that many ingenol compounds derived from Euphorbia kansui exhibit topoisomerase inhibitory activity and/or inhibitory activity of cell proliferation. The inhibitory effects of 20-O-(2'E,4'Z-decadienoyl) ingenol and 3-O-(2'E,4'Z-decadienoyl)-ingenol among these compounds on topoisomerase II activity and on the cell proliferative activity and arrest phase of the cell cycle were studied using a mouse breast cancer (MMT) cell line. Although 20-O-ingenolEZ exerted inhibitory effects on both topoisomerase II activity and cell proliferative activity, 3-O-ingenolEZ exerted inhibitory activity on neither. The 20-O-ingenolEZ-induced cell arrest of MMT-cell proliferation led to a cell cycle arrest in the G2/M phase. Topoisomerase II inhibition can be divided into the poison and catalytic inhibitor types. A checkpoint mechanism is activated when cells are treated with these topoisomerase II inhibitors. Poison-type inhibition occurs via induction of the DNA damage checkpoint and the catalytic-type inhibition occurs via induction of the DNA-decatenation checkpoint, suggestive of distinct checkpoint reactions. 20-O-ingenolEZ inhibited topoisomerase IIalpha activity through inhibition of ATPase, and induced DNA-decatenation checkpoint without signaling for phosphorylation of H2AX.
Authors:
Chisato Yoshida; Kazsuyoshi Hishiyama; Khosuke Miyazaki; Manami Watanabe; Masahiro Kanbe; Yuta Yamada; Keiithi Matsuzaki; Kiichi Miyashita; Susumu Kitanaka; Shohei Miyata
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cancer science     Volume:  101     ISSN:  1349-7006     ISO Abbreviation:  Cancer Sci.     Publication Date:  2010 Feb 
Date Detail:
Created Date:  2010-02-23     Completed Date:  2010-03-16     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101168776     Medline TA:  Cancer Sci     Country:  England    
Other Details:
Languages:  eng     Pagination:  374-8     Citation Subset:  IM    
Affiliation:
Department of Chemistry, College of Humanities and Sciences, Nihon University, Tokyo, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, Neoplasm
Antineoplastic Agents, Phytogenic / pharmacology*
Cell Division / drug effects
Cell Line, Tumor
Cell Proliferation / drug effects
DNA Topoisomerases, Type II, Eukaryotic / antagonists & inhibitors*
DNA-Binding Proteins / antagonists & inhibitors*
Diterpenes / pharmacology
Enzyme Inhibitors / pharmacology*
Euphorbia / chemistry
G2 Phase / drug effects
Mice
Chemical
Reg. No./Substance:
0/Antigens, Neoplasm; 0/Antineoplastic Agents, Phytogenic; 0/DNA-Binding Proteins; 0/Diterpenes; 0/Enzyme Inhibitors; 30220-46-3/ingenol; EC 5.99.1.-/DNA Topoisomerases, Type II, Eukaryotic; EC 5.99.1.3/DNA topoisomerase II alpha

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