title: Anticancer activity of 7,8-dihydroxyflavone in melanoma cells via downregulation of α-MSH/cAMP/MITF pathway.
abstract: Malignant melanoma is one of the most aggressive skin cancer and highly resistant to most conventional treatment. In the present study, we aimed to investigate the anticancer effects and mechanisms of action of 7,8-dihydroxyflavone (7,8-DHF), a monophenolic flavone, in melanoma cells. At concentrations not exhibiting cytotoxicity, 7,8-DHF potently inhibited growth and clonogenic survival of alpha-melanocyte stimulating hormone (α-MSH)-stimulated B16F10 melanoma cells. Furthermore, it significantly blocked migration and invasion of the metastatic melanoma cells. We also observed that 7,8-DHF exhibits anti-melanogenic activity through inhibition of tyrosinase activity in α-MSH-stimulating condition. Notably, the suppressive activities of 7,8-DHF on melanoma progression were associated with the downregulation of microphthalmia-associated transcription factor (MITF) and its main downstream transcription targets, including hypoxia-inducible factor 1α (HIF1α) and c-MET, by a decrease in cyclic adenosine monophosphate (cAMP) level. In addition, combination treatment with 7,8-DHF and resveratrol, a known therapeutic agent against melanoma, had greater anticancer activities and MITF inhibition than treatment with each single agent in α-MSH-treated B16F10 cells. Collectively, these findings may contribute to the potential application of 7,8-DHF in the prevention and treatment of malignant melanoma.
authors.affiliation: Department of BT-Convergent Pharmaceutical Engineering, Sun Moon University, Chungnam 336-708, Republic of Korea.
authors.forename: Deok Yong
authors.initials: DY
authors.lastname: Sim
authors.affiliation: Department of BT-Convergent Pharmaceutical Engineering, Sun Moon University, Chungnam 336-708, Republic of Korea.
authors.forename: Jae Kyung
authors.initials: JK
authors.lastname: Sohng
authors.affiliation: Department of BT-Convergent Pharmaceutical Engineering, Sun Moon University, Chungnam 336-708, Republic of Korea.
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Jung
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D000242:Cyclic AMP / Q000235:genetics*; D015536:Down-Regulation / Q000187:drug effects* / Q000235:genetics; D047309:Flavones / Q000494:pharmacology*; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000235:genetics; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics; D000521:alpha-MSH / Q000235:genetics*
chemical_list: C485383:6,7-dihydroxyflavone; D000970:Antineoplastic Agents; D047309:Flavones; D051739:Microphthalmia-Associated Transcription Factor; C497235:Mitf protein, mouse; D000521:alpha-MSH; D000242:Cyclic AMP