title: Anticancer effects of anandamide on head and neck squamous cell carcinoma cells via the production of receptor-independent reactive oxygen species.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  These findings suggest that AEA might have anticancer effects on HNSCC cells by mediating an increase in ROS levels through a receptor-independent mechanism.
authors.affiliation: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Seok-Woo
authors.initials: SW
authors.lastname: Park
authors.affiliation: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Ji-Eun
authors.initials: JE
authors.lastname: Kim
authors.affiliation: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Sang-Mi
authors.initials: SM
authors.lastname: Oh
authors.affiliation: Department of Otorhinolaryngology, Seoul National University Hospital, Seoul, Korea.
authors.forename: Won-Jae
authors.initials: WJ
authors.lastname: Cha
authors.affiliation: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.|Department of Otorhinolaryngology, Seoul National University Hospital, Seoul, Korea.|Clinical Research Institute, Seoul National University Hospital, Seoul, Korea.
authors.forename: Jeong-Hun
authors.initials: JH
authors.lastname: Hah
authors.affiliation: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.|Department of Otorhinolaryngology, Seoul National University Hospital, Seoul, Korea.|Clinical Research Institute, Seoul National University Hospital, Seoul, Korea.|Sensory Organ Research Institute, Seoul National University Medical Research Center, Seoul National University Hospital, Seoul, Korea.
authors.forename: Myung-Whun
authors.initials: MW
authors.lastname: Sung
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001095:Arachidonic Acids / Q000494:pharmacology*; D063386:Cannabinoid Receptor Agonists / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D063388:Endocannabinoids / Q000494:pharmacology*; D005989:Glycerides / Q000494:pharmacology; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D053284:Polyunsaturated Alkamides / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D001095:Arachidonic Acids; D063386:Cannabinoid Receptor Agonists; D063388:Endocannabinoids; D005989:Glycerides; D053284:Polyunsaturated Alkamides; D017382:Reactive Oxygen Species; C094503:glyceryl 2-arachidonate; C078814:anandamide
keywords: anandamide; anticancer agents; endocannabinoids; head and neck cancer; reactive oxygen species