Document Detail


The topoisomerase II-inhibitor NC-190 reduces the level of thymidine kinase mRNA in murine tumor cells.
MedLine Citation:
PMID:  14632316     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The novel antitumor compound NC-190 strongly inhibited the growth of FM3A cells with an IC50 of 0.019 microg/ml (0.042 microM) when cultured with NC-190 for 48 h. NC-190 potently suppressed DNA synthesis, with 90% inhibition observed at 0.1 microg/ml of NC-190. RNA and protein syntheses were also suppressed under the same conditions, but to a lesser extent. We then measured the cellular enzymatic activities of DNA polymerase alpha, RNA polymerase, thymidine kinase, thymidylate synthase and Leu-tRNA synthetase of FM3A cells cultured with or without NC-190. Of these 5 enzymes, the activity of thymidine kinase was most strongly suppressed by NC-190, by 77%. Although NC-190 did not directly inhibit the activitiy of thymidine kinase in a cell-free system, expression of mRNA of thymidine kinase was suppressed by 75% in NC-190-treated cells. These results indicate that NC-190 can suppress the expression of the gene for thymidine kinase and the inhibition of thymidine kinase contributes to the inhibition of cell growth by NC-190 together with the inhibition of topoisomerase II.
Authors:
Kazunori Samata; Takehiro Yamagishi; Tomotake Ikeda; Aiko Kuraishi; Shiro Nakaike; Makoto Tanaka; Keiko Kashiwagi; Kazuei Igarashi
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Research communications in molecular pathology and pharmacology     Volume:  111     ISSN:  1078-0297     ISO Abbreviation:  Res. Commun. Mol. Pathol. Pharmacol.     Publication Date:  2002  
Date Detail:
Created Date:  2003-11-24     Completed Date:  2004-07-20     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9437512     Medline TA:  Res Commun Mol Pathol Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  77-87     Citation Subset:  IM    
Affiliation:
Medicinal Research Laboratories, Taisho Pharmaceutical. Co., Ltd., 1-403, Yoshino-cho, Saitama-shi, Saitama 330-8530, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Cycle
Cell Division
Cell Line, Tumor
DNA Topoisomerases, Type II / antagonists & inhibitors*
Enzyme Inhibitors / pharmacology*
Mammary Neoplasms, Experimental / enzymology,  pathology
Mice
Phenazines / pharmacology*
RNA, Messenger / genetics,  metabolism*
Thymidine Kinase / genetics*
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Phenazines; 0/RNA, Messenger; 120602-99-5/NC 190; EC 2.7.1.21/Thymidine Kinase; EC 5.99.1.3/DNA Topoisomerases, Type II

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