title: Citrus flavanone naringenin enhances melanogenesis through the activation of Wnt/β-catenin signalling in mouse melanoma cells.
abstract: Citrus fruits are the major source of flavonoids for humans, and flavanones are the main flavonoids in the Citrus species. Among the Citrus flavanones, the glycoside derivatives of naringenin, naringin and narirutin, are the most abundant in grapefruit. The present study aimed to investigate the molecular events of melanogenesis induced by naringenin in murine B16-F10 melanoma cells. Melanin content, tyrosinase activity and Western blot analysis were performed to elucidate the possible underlying mechanisms. Exposure of melanoma cells to naringenin resulted in morphological changes accompanied by the induction of melanocyte differentiation-related markers, such as melanin synthesis, tyrosinase activity, and the expression of tyrosinase and microphthalmia-associated transcription factor (MITF). We also observed an increase in the intracellular accumulation of β-catenin as well as the phosphorylation of glycogen synthase kinase-3β (GSK3β) protein after treatment with naringenin. Moreover, the activity of phosphatidylinositol 3-kinase (PI3K) was up-regulated by naringenin since the phosphorylated level of downstream Akt protein was enhanced. Based on these results, we concluded that naringenin induced melanogenesis through the Wnt-β-catenin-signalling pathway.
authors.affiliation: Department of Cosmetic Science, Providence University, Taichung, Taiwan, ROC. ychuang@pu.edu.tw
authors.forename: Yu-Chun
authors.initials: YC
authors.lastname: Huang
authors.forename: Chao-Hsun
authors.initials: CH
authors.lastname: Yang
authors.forename: Yi-Ling
authors.initials: YL
authors.lastname: Chiou
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002470:Cell Survival; D002867:Chromones / Q000494:pharmacology; D002957:Citrus / Q000737:chemistry*; D044950:Flavanones / Q000494:pharmacology*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D008543:Melanins / Q000378:metabolism; D008544:Melanocytes / Q000187:drug effects; D008546:Melanoma, Experimental / Q000201:enzymology; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor / Q000378:metabolism; D014442:Monophenol Monooxygenase / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D010858:Pigmentation / Q000187:drug effects*; D015854:Up-Regulation; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism
chemical_list: C495267:CTNNB1 protein, mouse; D002867:Chromones; D044950:Flavanones; D008543:Melanins; D051739:Microphthalmia-Associated Transcription Factor; C497235:Mitf protein, mouse; D009025:Morpholines; D051176:beta Catenin; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D014442:Monophenol Monooxygenase; D019869:Phosphatidylinositol 3-Kinases; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3; C005273:naringenin