The Endocannabinoid System as a Target for Treatment of Breast Cancer
Final rept. 1 Aug 2008-31 Jul 2011
VIRGINIA COMMONWEALTH UNIV RICHMOND
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During this project period, we employed in vivo and in vitro approaches to determine whether the endogenous cannabinoid system can be targeted to treat breast cancer. The first objective of this work was to develop a preclinical model to induce mammary tumors in mice and determine whether elevating levels of the endogenous cannabinoid anandamide through the use of mice lacking fatty acid amide hydrolase FAAH, the primary catabolic enzyme responsible for degrading this endogenous cannabinoid, would show decreased tumorigenesis. The carcinogen, DMBA, produced the appearance of tumors in the mammary region of female control C57Bl6 mice and FAAH knockout mice. However, the tumors could not be conclusively identified as being breast cancer. The second objective of this project was to evaluate interactions of cannabinoids with radiation in MCF-7, MDA-MB-231, and 4T1 breast tumor cell lines. Interestingly, the high efficacy synthetic cannabinoid agonist WIN55,212-2, but not its stereoisomer WIN55,212-3 or the phytocannabinoids 9-tetrahydrocannabinol THC or cannabidiol CBD, significantly enhanced the effects of radiation in decreasing cell viability. The enhanced effects of combination of WIN55,212-2 and radiation on breast cancer suggest the possibility that this type of strategy many hold promise to treat this disease.
- Anatomy and Physiology
- Medicine and Medical Research