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Delta9-tetrahydrocannabinol inhibits cell cycle progression in human breast cancer cells through Cdc2 regulation.
Cancer Res. 2006 Jul 01; 66(13):6615-21.CR

Abstract

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.

Authors+Show Affiliations

Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, 28040 Madrid, Spain.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16818634

Citation

Caffarel, María M., et al. "Delta9-tetrahydrocannabinol Inhibits Cell Cycle Progression in Human Breast Cancer Cells Through Cdc2 Regulation." Cancer Research, vol. 66, no. 13, 2006, pp. 6615-21.
Caffarel MM, Sarrió D, Palacios J, et al. Delta9-tetrahydrocannabinol inhibits cell cycle progression in human breast cancer cells through Cdc2 regulation. Cancer Res. 2006;66(13):6615-21.
Caffarel, M. M., Sarrió, D., Palacios, J., Guzmán, M., & Sánchez, C. (2006). Delta9-tetrahydrocannabinol inhibits cell cycle progression in human breast cancer cells through Cdc2 regulation. Cancer Research, 66(13), 6615-21.
Caffarel MM, et al. Delta9-tetrahydrocannabinol Inhibits Cell Cycle Progression in Human Breast Cancer Cells Through Cdc2 Regulation. Cancer Res. 2006 Jul 1;66(13):6615-21. PubMed PMID: 16818634.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Delta9-tetrahydrocannabinol inhibits cell cycle progression in human breast cancer cells through Cdc2 regulation. AU - Caffarel,María M, AU - Sarrió,David, AU - Palacios,José, AU - Guzmán,Manuel, AU - Sánchez,Cristina, PY - 2006/7/5/pubmed PY - 2006/9/8/medline PY - 2006/7/5/entrez SP - 6615 EP - 21 JF - Cancer research JO - Cancer Res VL - 66 IS - 13 N2 - 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. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/16818634/Delta9_tetrahydrocannabinol_inhibits_cell_cycle_progression_in_human_breast_cancer_cells_through_Cdc2_regulation_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=16818634 DB - PRIME DP - Unbound Medicine ER -