Anticancer effects of anandamide on head and neck squamous cell carcinoma cells via the production of receptor-independent reactive oxygen species

Background The endocannabinoids, anandamide (AEA) and 2‐arachidonoyl glycerol (2‐AG), are considered promising potential anticancer agents. In this study, we examined the anticancer effects of AEA and 2‐AG in head and neck squamous cell carcinoma (HNSCC) cell lines. Methods and Results Our results showed that AEA effectively inhibited proliferation of HNSCC cells whereas 2‐AG did not. The anticancer effect of AEA seemed to be mediated by a receptor‐independent mechanism. Inhibitors of AEA intracellular transportation and transfection of HNSCC cells with fatty acid amide hydrolase, a key enzyme in AEA metabolism, reversed AEA‐dependent inhibition of cell proliferation. We found that cyclooxygenase‐2 (COX‐2) did not mediate the anticancer effects of AEA; instead we observed an increase in reactive oxygen species (ROS) production after AEA treatment. Moreover, antioxidants partially reversed AEA‐dependent inhibition of cell proliferation. Conclusion These findings suggest that AEA might have anticancer effects on HNSCC cells by mediating an increase in ROS levels through a receptor‐independent mechanism. © 2014 Wiley Periodicals, Inc. Head Neck 37: 1187–1192, 2015