| Modulation of Delta9-tetrahydrocannabinol-induced MCF-7 breast cancer cell growth by cyclooxygenase and aromatase. | |
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MedLine Citation:
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PMID: 19428940 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Shuso Takeda; Ikuo Yamamoto; Kazuhito Watanabe |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-02-04 |
Journal Detail:
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Title: Toxicology Volume: 259 ISSN: 0300-483X ISO Abbreviation: Toxicology Publication Date: 2009 May |
Date Detail:
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Created Date: 2009-05-11 Completed Date: 2009-06-02 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0361055 Medline TA: Toxicology Country: Ireland |
Other Details:
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Languages: eng Pagination: 25-32 Citation Subset: IM |
Affiliation:
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Organization for Frontier Research in Preventive Pharmaceutical Sciences, Hokuriku University, Ho-3 Kanagawa-machi, Kanazawa 920-1181, Japan. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Arachidonic Acid
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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 Female Gene Expression Regulation, Enzymologic Humans Signal Transduction / drug effects Tetrahydrocannabinol / toxicity* |
| Chemical | |
Reg. No./Substance:
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0/Cyclooxygenase 2 Inhibitors; 1972-08-3/Tetrahydrocannabinol; 363-24-6/Dinoprostone; 50-28-2/Estradiol; 506-32-1/Arachidonic Acid; EC 1.14.14.1/Aromatase; EC 1.14.99.1/Cyclooxygenase 2 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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