| Delta9-tetrahydrocannabinol inhibits cell cycle progression in human breast cancer cells through Cdc2 regulation. | |
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MedLine Citation:
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PMID: 16818634 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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It has been proposed that cannabinoids are involved in the control of cell fate. Thus, these compounds can modulate proliferation, differentiation, and survival in different manners depending on the cell type and its physiopathologic context. However, little is known about the effect of cannabinoids on the cell cycle, the main process controlling cell fate. Here, we show that Delta(9)-tetrahydrocannabinol (THC), through activation of CB(2) cannabinoid receptors, reduces human breast cancer cell proliferation by blocking the progression of the cell cycle and by inducing apoptosis. In particular, THC arrests cells in G(2)-M via down-regulation of Cdc2, as suggested by the decreased sensitivity to THC acquired by Cdc2-overexpressing cells. Of interest, the proliferation pattern of normal human mammary epithelial cells was much less affected by THC. We also analyzed by real-time quantitative PCR the expression of CB(1) and CB(2) cannabinoid receptors in a series of human breast tumor and nontumor samples. We found a correlation between CB(2) expression and histologic grade of the tumors. There was also an association between CB(2) expression and other markers of prognostic and predictive value, such as estrogen receptor, progesterone receptor, and ERBB2/HER-2 oncogene. Importantly, no significant CB(2) expression was detected in nontumor breast tissue. Taken together, these data might set the bases for a cannabinoid therapy for the management of breast cancer. |
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Authors:
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María M Caffarel; David Sarrió; José Palacios; Manuel Guzmán; Cristina Sánchez |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Cancer research Volume: 66 ISSN: 0008-5472 ISO Abbreviation: Cancer Res. Publication Date: 2006 Jul |
Date Detail:
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Created Date: 2006-07-04 Completed Date: 2006-09-07 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 2984705R Medline TA: Cancer Res Country: United States |
Other Details:
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Languages: eng Pagination: 6615-21 Citation Subset: IM |
Affiliation:
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Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, 28040 Madrid, Spain. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis
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drug effects Breast Neoplasms / drug therapy, enzymology, metabolism, pathology* CDC2 Protein Kinase / biosynthesis*, genetics Cell Cycle / drug effects* Cell Division / drug effects Cell Growth Processes / drug effects Cell Line, Tumor Down-Regulation / drug effects G2 Phase / drug effects Humans RNA, Messenger / biosynthesis, genetics Receptor, Cannabinoid, CB1 / biosynthesis, genetics Receptor, Cannabinoid, CB2 / biosynthesis, genetics Tetrahydrocannabinol / pharmacology* |
| Chemical | |
Reg. No./Substance:
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0/RNA, Messenger; 0/Receptor, Cannabinoid, CB1; 0/Receptor, Cannabinoid, CB2; 1972-08-3/Tetrahydrocannabinol; EC 2.7.11.22/CDC2 Protein Kinase |
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