Document Detail


Inhibitory effects of docosyl p-coumarate on DNA topoisomerase activity and human cancer cell growth.
MedLine Citation:
PMID:  20811721     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We previously found six compounds of alkyl p-coumarates from a composite plant Artemisia annua L., and chemically synthesized these compounds (cis-isomer of C20, C22 and C24, and trans-isomer of C20, C22 and C24 of p-coumarates are compounds 1-6, respectively). This report describes the inhibitory activities of these alkyl p-coumarates against DNA polymerase (pol), DNA topoisomerase (topo), and human cancer cell growth. Among the compounds tested, compounds 1 and 4 weakly inhibited repair-related pol beta activity, but no compound influenced the activity of replicative pol alpha. Compounds 4-6 and compounds 2 and 5 were potent inhibitors of human topos I and II, respectively. Compounds 2, 4, 5 and 6 also suppressed the growth of human colon carcinoma cell line, HCT116, with or without p53, suggesting that cell growth inhibition had the same tendency as the inhibition of topos rather than pols. Compound 5 (docosyl p-coumarate), which was the strongest inhibitor of topo II and cancer cell growth in the compounds tested, halted HCT116 p53(+/+) cells in G2/M phases, and induced apoptosis, although this compound did not affect the cell cycle of HCT116 p53(-/-) cells. These results suggest that the effect of p53-dependent cell cycle arrest may be effective for topo inhibition by com-pound 5. From these findings, the action mode of alkyl p-coumarates as an anti-cancer agent is discussed.
Authors:
Yoshiyuki Mizushina; Katsumi Nishimura; Yukiko Takenaka; Toshifumi Takeuchi; Fumio Sugawara; Hiromi Yoshida; Takao Tanahashi
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of oncology     Volume:  37     ISSN:  1791-2423     ISO Abbreviation:  Int. J. Oncol.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-09-02     Completed Date:  2010-12-23     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9306042     Medline TA:  Int J Oncol     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  993-1000     Citation Subset:  IM    
Affiliation:
Laboratory of Food & Nutritional Sciences, Department of Nutritional Science, Kobe-Gakuin University, Nishi-ku, Kobe, Hyogo 651-2180, Japan. mizushin@nutr.kobegakuin.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents, Phytogenic / pharmacology*
Apoptosis / drug effects
Cell Cycle / drug effects
Cell Proliferation / drug effects*
Colonic Neoplasms / enzymology*,  genetics,  pathology*
Coumaric Acids / pharmacology*
DNA Topoisomerases, Type I / metabolism*
Dose-Response Relationship, Drug
HCT116 Cells
Humans
Inhibitory Concentration 50
Time Factors
Topoisomerase Inhibitors / pharmacology*
Tumor Suppressor Protein p53 / genetics,  metabolism
Chemical
Reg. No./Substance:
0/Antineoplastic Agents, Phytogenic; 0/Coumaric Acids; 0/TP53 protein, human; 0/Topoisomerase Inhibitors; 0/Tumor Suppressor Protein p53; 0/docosyl 4-coumarate; EC 5.99.1.2/DNA Topoisomerases, Type I

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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