Inhibiting Fatty Acid Amide Hydrolase (FAAH) Induces Apoptosis in Breast Cancer Cells



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Background: Breast cancer is a highly heterogeneous, aggressive disease that has poor prognosis. Current treatment is present, but research on a therapeutic alternative is ongoing. Endocannabinoids, members of the endocannabinoid system, are naturally produced by cells in our bodies. They are diverse signaling components that have several functions, including regulation of the apoptosis mechanism. Fatty Acid Amide Hydrolase (FAAH) is an integral membrane enzyme that hydrolyzes endocannabinoids, rendering them inactive. Since FAAH is upregulated in cancer cells, FAAH inhibition is predicted to increase the apoptotic rate. Methods: To test the effects of FAAH inhibitors and exogenous endocannabinoids, cells were cultured, probed for FAAH expression using Western blot analysis, treated with FAAH inhibitors, exogenous endocannabinoids, and combinations of both, all in varying doses, and cell viability was measured using MTT assays. Results: High levels of FAAH were observed in two breast cancer cell lines. The greatest change was observed at 50 μm PF-750 treatment, which is the most selective FAAH inhibitor. URB597 combination treatments decreased cell viability in a supra-additive manner. The most significant change was observed at co-treatment levels of 50 μm URB597 and 50 μm AEA, which resulted in a 30% decrease (p<0.001) in cell viability compared to vehicle control. FAAH inhibition was more effective than exogenous endocannabinoid use, and combination treatments of FAAH inhibitors and exogenous endocannabinoids, both at the highest doses, were the most effective.