title: Arachidonyl ethanolamide induces apoptosis of uterine cervix cancer cells via aberrantly expressed vanilloid receptor-1.
abstract: 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 CB1 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Oncology Division, Laboratory of Tumor Immunology, University Hospital, Geneva, Switzerland.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Contassot
authors.forename: Mirna
authors.initials: M
authors.lastname: Tenan
authors.forename: Valérie
authors.initials: V
authors.lastname: Schnüriger
authors.forename: Marie-Françoise
authors.initials: MF
authors.lastname: Pelte
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Dietrich
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001095:Arachidonic Acids / Q000494:pharmacology*; D063385:Cannabinoid Receptor Modulators / Q000494:pharmacology*; D045744:Cell Line, Tumor; D063388:Endocannabinoids; D005260:Female; D006367:HeLa Cells; D006801:Humans; D053284:Polyunsaturated Alkamides; D043884:Receptor, Cannabinoid, CB1 / Q000096:biosynthesis / Q000502:physiology; D043885:Receptor, Cannabinoid, CB2 / Q000096:biosynthesis / Q000502:physiology; D011955:Receptors, Drug / Q000096:biosynthesis / Q000502:physiology*; D050916:TRPV Cation Channels; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*
chemical_list: D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D011955:Receptors, Drug; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; C078814:anandamide