NDLI: Anti-melanogenic effects of Î´-tocotrienol are associated with tyrosinase-related proteins and MAPK signaling pathway in B16 melanoma cells.

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Anti-melanogenic effects of Î´-tocotrienol are associated with tyrosinase-related proteins and MAPK signaling pathway in B16 melanoma cells.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Ng, Lean-Teik Lin, Liang-Tzung Chen, Chiu-Lan Chen, Hsiu-Wen Wu, Shu-Jing Lin, Chun-Ching
Description	Country affiliation: Taiwan Author Affiliation: Ng LT ( Department of Agricultural Chemistry, National Taiwan University, Taipei, Taiwan.); Lin LT ( Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.); Chen CL ( Department of Pharmacy, Chia-Nan University of Pharmacy and Science, Tainan, Taiwan.); Chen HW ( Department of Nutritional Health, Chia-Nan University of Pharmacy and Science, Tainan, Taiwan.); Wu SJ ( Department of Nutritional Health, Chia-Nan University of Pharmacy and Science, Tainan, Taiwan. Electronic address: wsj268@mail.chna.edu.tw.); Lin CC ( Faculty of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address: aalin@kmu.edu.tw.)
Abstract	Tocotrienols are known to possess potent antioxidant, anticancer, and cholesterol lowering activities. Being able to rapidly penetrate the skin, these vitamin E isoforms have been explored for potential treatment against melanoma. This study aimed to elucidate the mechanism involved in the anti-melanogenic effects of Î´-tocotrienol (Î´T3) in B16 melanoma cells. Results showed that at 20 µM of Î´T3 significantly inhibited melanin formation and ROS generation. Treatment with Î´T3 also effectively suppressed the expression of melanogenesis-related proteins, including MC1R, MITF, TYRP-1, and TYRP-2. More importantly, we observed that the mitogen-activated protein kinase (MAPK) pathway was involved in mediating Î´T3's inhibitory effect against melanin production. Specifically, Î´T3 treatment markedly induced the activation of extracellular signal-regulated kinases (ERK). The use of ERK activation inhibitor (PD98059) abrogated the Î´T3-mediated downregulation expression melanogenesis-related proteins and restored melanin production. Furthermore, siRNA targeting ERK effectively blocked the Î´T3-induced repression of tyrosinase and TYRP-1 expression. These results suggest that Î´T3's inhibitory effect against melanogenesis is mediated by the activation of ERK signaling, thereby resulting in downstream repression of melanogenesis-related proteins and the subsequent melanin production. These data provide insight to Î´T3's effect and the targeting of ERK signaling for treatment against melanogenesis.
File Format	HTM / HTML
ISSN	09447113
Issue Number	7
Volume Number	21
e-ISSN	1618095X
Journal	Phytomedicine
Language	English
Publisher	Elsevier
Publisher Date	2014-06-15
Publisher Place	Germany
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Discipline Complementary Therapies Map Kinase Signaling System Drug Effects Melanins Metabolism Melanoma, Experimental Drug Therapy Vitamin E Analogs & Derivatives Animals Cell Line, Tumor Cell Survival Flavonoids Pharmacology Indoles Intramolecular Oxidoreductases Pathology Membrane Glycoproteins Mice Microphthalmia-associated Transcription Factor Oxidoreductases Protein Kinase Inhibitors Reactive Oxygen Species Journal Article
Content Type	Text
Resource Type	Article
Subject	Drug Discovery Molecular Medicine Pharmacology Complementary and Alternative Medicine Pharmaceutical Science

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