title: A derivative of 2-aminothiazole inhibits melanogenesis in B16 mouse melanoma cells via glycogen synthase kinase 3β phosphorylation.
abstract: OBJECTIVE
  We have investigated whether KHG25855 (2-cyclohexylamino-1,3-thiazole hydrochloride) affected melanogenesis in B16 mouse melanoma cells, and the mechanisms involved.
  
  
  METHODS
  Melanin content and tyrosinase activity were measured using an ELISA reader after cells were treated with KHG25855. KHG25855-induced signalling pathways were examined using Western blot analysis.
  
  
  RESULTS
  KHG25855 decreased melanin production in a dose-dependent fashion, but KHG25855 did not directly inhibit tyrosinase, the rate-limiting melanogenic enzyme. The expression of microphthalmia-associated transcription factor, tyrosinase, and the related signal transduction pathways were also investigated. The effects of KHG25855 on the extracellular signal-regulated kinase and cAMP response element binding protein signalling pathways were determined, and KHG25855 was shown to have no effect on these signalling pathways. The Wnt signalling pathway is also deeply involved in melanogenesis, and so glycogen synthase kinase 3β (GSK3β) phosphorylation was assessed after KHG25855 treatment; KHG25855 caused GSK3β phosphorylation (inactivation), but the level of β-catenin was not changed by KHG25855. Furthermore, α-melanocyte stimulating hormone-induced tyrosinase expression was downregulated by KHG25855.
  
  
  CONCLUSIONS
  We propose that KHG25855 showed hypopigmentary activity through tyrosinase downregulation via GSK3β phosphorylation.
authors: Department of Biochemistry, Chung-Ang University College of Medicine, Seoul, Korea.
authors: Su Yeon
authors: SY
authors: Kim
authors: Hoh-Gyu
authors: HG
authors: Hahn
authors: Kee Dal
authors: KD
authors: Nam
authors: Kyoung-Chan
authors: KC
authors: Park
authors: Hye-Young
authors: HY
authors: Yun
authors: Kwang Jin
authors: KJ
authors: Baek
authors: Nyoun Soo
authors: NS
authors: Kwon
authors: Dong-Seok
authors: DS
authors: Kim
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D038341:Glycogen Synthase Kinases / Q000378:metabolism*; D008543:Melanins / Q000096:biosynthesis*; D008546:Melanoma, Experimental / Q000378:metabolism*; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor / Q000378:metabolism; D014442:Monophenol Monooxygenase / Q000378:metabolism*; D010766:Phosphorylation; D015398:Signal Transduction / Q000187:drug effects; D013844:Thiazoles / Q000494:pharmacology*; D051153:Wnt Proteins / Q000378:metabolism; D000521:alpha-MSH / Q000378:metabolism
chemical_list: D008543:Melanins; D051739:Microphthalmia-Associated Transcription Factor; D013844:Thiazoles; D051153:Wnt Proteins; D000521:alpha-MSH; C004483:2-aminothiazole; D014442:Monophenol Monooxygenase; D038341:Glycogen Synthase Kinases