title: N-(4-methoxyphenyl) caffeamide-induced melanogenesis inhibition mechanisms.
abstract: BACKGROUND
  The derivative of caffeamide exhibits antioxidant and antityrosinase activity. The activity and mechanism of N-(4-methoxyphenyl) caffeamide (K36E) on melanogenesis was investigated.
  
  
  METHODS
  B16F0 cells were treated with various concentrations of K36E; the melanin contents and related signal transduction were studied. Western blotting assay was applied to determine the protein expression, and spectrophotometry was performed to identify the tyrosinase activity and melanin content.
  
  
  RESULTS
  Our results indicated that K36E reduced α-melanocyte-stimulating hormone (α-MSH)-induced melanin content and tyrosinase activity in B16F0 cells. In addition, K36E inhibited the expression of phospho-cyclic adenosine monophosphate (cAMP)-response element-binding protein, microphthalmia-associated transcription factor (MITF), tyrosinase, and tyrosinase-related protein-1 (TRP-1). K36E activated the phosphorylation of protein kinase B (AKT) and glycogen synthase kinase 3 beta (GSK3β), leading to the inhibition of MITF transcription activity. K36E attenuated α-MSH induced cAMP pathways, contributing to hypopigmentation.
  
  
  CONCLUSIONS
  K36E regulated melanin synthesis through reducing the expression of downstream proteins including p-CREB, p-AKT, p-GSK3β, tyrosinase, and TRP-1, and activated the transcription factor, MITF. K36E may have the potential to be developed as a skin whitening agent.
authors.affiliation: Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung, 404, Taiwan.|Department of Biotechnology, Asia University, Taichung, 413, Taiwan.
authors.forename: Yueh-Hsiung
authors.initials: YH
authors.lastname: Kuo
authors.affiliation: Department of Cosmeceutics, China Medical University, Taichung, 404, Taiwan.
authors.forename: Chien-Chia
authors.initials: CC
authors.lastname: Chen
authors.affiliation: Department of Dermatology, China Medical University Hospital, Taichung, 404, Taiwan.|School of Medicine, China Medical University, Taichung, 404, Taiwan.
authors.forename: Po-Yuan
authors.initials: PY
authors.lastname: Wu
authors.affiliation: Department of Cosmeceutics, China Medical University, Taichung, 404, Taiwan.
authors.forename: Chin-Sheng
authors.initials: CS
authors.lastname: Wu
authors.affiliation: National Museum of Marine Biology and Aquarium, Pingtung, 944, Taiwan.
authors.forename: Ping-Jyun
authors.initials: PJ
authors.lastname: Sung
authors.affiliation: Department of Biotechnology, Asia University, Taichung, 413, Taiwan.
authors.forename: Chien-Yih
authors.initials: CY
authors.lastname: Lin
authors.affiliation: Department of Cosmeceutics, China Medical University, Taichung, 404, Taiwan. hmchiang@mail.cmu.edu.tw.
authors.forename: Hsiu-Mei
authors.initials: HM
authors.lastname: Chiang
mesh_terms: D000813:Anilides / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D002109:Caffeic Acids / Q000138:chemical synthesis / Q000494:pharmacology*; D045744:Cell Line, Tumor; D017362:Cyclic AMP Response Element-Binding Protein / Q000037:antagonists & inhibitors / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism; D007370:Interferon Type I / Q000037:antagonists & inhibitors / Q000378:metabolism; D008543:Melanins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D011257:Pregnancy Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D062327:Skin Lightening Preparations / Q000138:chemical synthesis
chemical_list: D000813:Anilides; D002109:Caffeic Acids; D017362:Cyclic AMP Response Element-Binding Protein; D007370:Interferon Type I; D008543:Melanins; D051739:Microphthalmia-Associated Transcription Factor; C497235:Mitf protein, mouse; C000614103:N-(4-methoxyphenyl)caffeamide; D011257:Pregnancy Proteins; D062327:Skin Lightening Preparations; C020947:interferon tau; D014442:Monophenol Monooxygenase; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt
keywords: Glycogen synthase kinase 3 beta; Melanogenesis; Microphthalmia-associated transcription factor; N-(4-methoxyphenyl) caffeamide; Propolis; cAMP response element-binding protein