title: Induction of melanogenesis by 4'-O-methylated flavonoids in B16F10 melanoma cells.
abstract: Agents to control melanogenesis are in demand for the development of cosmetics to improve pigmentation disorders of skin and hair. In this study, we examined and evaluated the effects of flavonoids on melanogenesis in the melanogenic cells model, murine B16F10 melanoma cells. In the course of this study, we found that incubation of the cells in a medium containing 10 μM of the 4'-O-methylated flavonoids, diosmetin (4'-O-methylluteolin), acacetin (4'-O-methylapigenin) or kaempferide (4'-O-methylkaempferol), increased the melanin contents of the cells 3- to 7-fold higher than the control cells. The concentration-dependence test revealed that 20 μM acacetin showed the highest effect, up to 33-fold higher than the vehicle. On the other hand, the corresponding 4'-OH-type flavonoids, luteolin, apigenin and kaempferol, had a significantly smaller effect. Furthermore, by evaluating the melanogenic proteins, we found that the cells treated with 4'-O-methylated flavonoids showed higher tyrosinase activity, as well as upregulation of tyrosinase expression, preceded by activation of cAMP response element binding protein (CREB) and extracellular signal-regulated kinases types 1 and 2 (ERK1/2). These results indicate that the 4'-O-methyl group of flavonoids plays an important role in the induction of melanogenesis by activating its major signal transduction pathway through the upregulation of phospho-CREB in murine B16F10 melanoma cells.
authors.affiliation: Nakano Seiyaku Co. Ltd, 6-20 Kitainoue-cho, Higashino, Yamashina-ku, Kyoto, 607-8141, Japan.
authors.forename: Ippei
authors.initials: I
authors.lastname: Horibe
authors.forename: Yudai
authors.initials: Y
authors.lastname: Satoh
authors.forename: Yuki
authors.initials: Y
authors.lastname: Shiota
authors.forename: Ayako
authors.initials: A
authors.lastname: Kumagai
authors.forename: Nanao
authors.initials: N
authors.lastname: Horike
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takemori
authors.forename: Shinichi
authors.initials: S
authors.lastname: Uesato
authors.forename: Shuji
authors.initials: S
authors.lastname: Sugie
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Obata
authors.forename: Hidehisa
authors.initials: H
authors.lastname: Kawahara
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Nagaoka
mesh_terms: D000818:Animals; D047310:Apigenin / Q000494:pharmacology; D045744:Cell Line, Tumor; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D047309:Flavones / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology*; D047311:Luteolin / Q000494:pharmacology; D008543:Melanins / Q000096:biosynthesis*; D008546:Melanoma, Experimental; D051379:Mice; D014442:Monophenol Monooxygenase / Q000378:metabolism
chemical_list: D047309:Flavones; D005419:Flavonoids; D008543:Melanins; D047310:Apigenin; D014442:Monophenol Monooxygenase; D048049:Extracellular Signal-Regulated MAP Kinases; D047311:Luteolin; C023717:acacetin; C039602:diosmetin