Document Detail

Modulation of Delta9-tetrahydrocannabinol-induced MCF-7 breast cancer cell growth by cyclooxygenase and aromatase.
MedLine Citation:
PMID:  19428940     Owner:  NLM     Status:  MEDLINE    
Delta(9)-Tetrahydrocannabinol (Delta(9)-THC), a major constituent of marijuana, has been shown to stimulate the growth of MCF-7 breast cancer cells through cannabinoid receptor-independent signaling [Takeda, S., Yamaori, S., Motoya, E., Matsunaga, T., Kimura, T., Yamamoto, I., Watanabe, K., 2008. Delta(9)-Tetrahydrocannabinol enhances MCF-7 cell proliferation via cannabinoid receptor-independent signaling. Toxicology 245, 141-146]. Although the growth of MCF-7 cells is known to be stimulated by 17beta-estradiol (E(2)), the interaction of Delta(9)-THC and E(2) in MCF-7 cell growth is not fully clarified so far. In the present study, by using E(2)-sensitive MCF-7 cells that have expressed cyclooxygenase-2 (COX-2) and cytochrome P450 19 (aromatase), we studied whether or not COX-2 and aromatase are involved in Delta(9)-THC-mediated MCF-7 cell proliferation. It was shown that Delta(9)-THC-induced MCF-7 cell growth was inhibited by COX-2 inhibitors and was stimulated by arachidonic acid (a COX substrate). However, the growth of MCF-7 cells induced by Delta(9)-THC was not stimulated by PGE(2), and the expression of aromatase was not affected by COX-2 inhibitors, arachidonic acid, and PGE(2), suggesting that there is a disconnection between COX-2 (PGE(2)) and aromatase in Delta(9)-THC-mediated MCF-7 cell proliferation. On the other hand, Delta(9)-THC-induced MCF-7 cell growth was elevated by two kinds of aromatase inhibitors. Taken together with the evidence that Delta(9)-THC-induced MCF-7 cell proliferation was interfered with testosterone (an aromatase substrate) and exogenously provided E(2), it is suggested that (1) the growth stimulatory effects of Delta(9)-THC are mediated by the product(s) of COX-2 except for PGE(2), (2) the action of Delta(9)-THC is modulated by E(2), and (3) COX-2 and aromatase are individually engaged in the proliferation of MCF-7 cells induced by Delta(9)-THC.
Shuso Takeda; Ikuo Yamamoto; Kazuhito Watanabe
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-02-04
Journal Detail:
Title:  Toxicology     Volume:  259     ISSN:  0300-483X     ISO Abbreviation:  Toxicology     Publication Date:  2009 May 
Date Detail:
Created Date:  2009-05-11     Completed Date:  2009-06-02     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0361055     Medline TA:  Toxicology     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  25-32     Citation Subset:  IM    
Organization for Frontier Research in Preventive Pharmaceutical Sciences, Hokuriku University, Ho-3 Kanagawa-machi, Kanazawa 920-1181, Japan.
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MeSH Terms
Arachidonic Acid / pharmacology
Aromatase / drug effects*,  metabolism
Breast Neoplasms / metabolism*,  pathology
Cannabis / chemistry
Cell Line, Tumor
Cell Proliferation / drug effects*
Cyclooxygenase 2 / drug effects*,  metabolism
Cyclooxygenase 2 Inhibitors / pharmacology
Dinoprostone / metabolism
Estradiol / metabolism,  pharmacology
Gene Expression Regulation, Enzymologic
Signal Transduction / drug effects
Tetrahydrocannabinol / toxicity*
Reg. No./Substance:
0/Cyclooxygenase 2 Inhibitors; 1972-08-3/Tetrahydrocannabinol; 363-24-6/Dinoprostone; 50-28-2/Estradiol; 506-32-1/Arachidonic Acid; EC; EC 2

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