Arachidonyl ethanolamide induces apoptosis of uterine cervix cancer cells via aberrantly expressed vanilloid receptor-1

Objective. Delta(9)-Tetrahydrocannabinol, the active agent of Cannabis sativa, exhibits well-documented antitumor properties, but little is known about the possible effects mediated by endogenous cannabinoids on human tumors. In the present study, we analyzed the effect of arachidonyl ethanolamide (AEA) on cervical carcinoma (CxCa) cell lines. Methods. To assess the sensitivity of CxCa cells to AEA, we selected three cell lines that were exposed to increasing doses of AEA with or without antagonists to receptors to AEA. DNA fragmentation and caspase-7 activity were used as apoptosis markers. The expression of receptors to AEA were analyzed in CxCa cell lines as well as CxCa biopsies. Results. The major finding was that AEA induced apoptosis of CxCa cell lines via aberrantly expressed vanilloid receptor-1, whereas AEA binding to the classical CBI and CB2 cannabinoid receptors mediated a protective effect. Furthermore, unexpectedly, a strong expression of the three forms of AEA receptors was observed in ex vivo CxCa biopsies. Conclusion. Overall, these data suggest that the specific targeting of VR1 by endogenous cannabinoids or synthetic molecules offers attractive opportunities for the development of novel potent anticancer drugs. (C) 2004 Elsevier Inc. All rights reserved.