title: (-)-Oleocanthal exerts anti-melanoma activities and inhibits STAT3 signaling pathway.
abstract: Tumor angiogenesis, growth and metastasis are three closely related processes. We therefore explored the effects of (-)-oleocanthal (OC) on the three processes in melanoma and investigated underlying mechanisms. In vitro, OC suppressed proliferation, migration, invasion and induced apoptosis in melanoma cells. In addition, OC inhibited proliferation, migration, invasion and tube formation in human umbilical vascular endothelial cells. In vivo, it exhibited potent activity in suppressing tumor growth in a subcutaneous xenograft model. Furthermore, OC suppressed proliferation and angiogenesis as measured by immunohistochemical staining of Ki-67 and CD31. In addition, OC was found to inhibit metastasis of melanoma in a lung metastasis model. Mechanistically, OC significantly suppressed signal transducer and activator of transcription 3 (STAT3) phosphorylation, decreased STAT3 nuclear localization and inhibited STAT3 transcriptional activity. OC also downregulated STAT3 target genes, including Mcl-1, Bcl-xL, MMP-2, MMP-9, VEGF, which are involved in apoptosis, invasion and angiogenesis of melanoma. These results support further investigation of OC as a potential anti-melanoma drug.
authors.affiliation: Department of Dermatology, Daqing Oilfield General Hospital, Saertu, Daqing, Heilongjiang 163001, P.R. China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Department of Dermatology, Daqing Oilfield General Hospital, Saertu, Daqing, Heilongjiang 163001, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Dermatology, Daqing Oilfield General Hospital, Saertu, Daqing, Heilongjiang 163001, P.R. China.
authors.forename: Lixin
authors.initials: L
authors.lastname: Peng
mesh_terms: D000447:Aldehydes / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D000081004:Cyclopentane Monoterpenes; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008297:Male; D008545:Melanoma / Q000098:blood supply / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000473:pathology / Q000517:prevention & control*; D010636:Phenols / Q000494:pharmacology*; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000447:Aldehydes; D000970:Antineoplastic Agents; D000081004:Cyclopentane Monoterpenes; D010636:Phenols; D050796:STAT3 Transcription Factor; C503534:oleocanthal