Anti-melanogenic effects of δ-tocotrienol are associated with tyrosinase-related proteins and MAPK signaling pathway in B16 melanoma cells |
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| Institution: | 1. Institute for Pharma Technology, School of Life Sciences, University of Applied Sciences Northwestern Switzerland, Gründenstrasse 40, CH-4132 Muttenz, Switzerland;2. Institute of Pharmaceutical Biology, Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, CH-4056, Basel, Switzerland;3. AgroBioInstitute, Agriculture Academy, Dragan Tzankov 8, Sofia 1164, Bulgaria;1. Department of Chinese Medicine, Chang Bing Show Chwan Memorial Hospital, Changhua, Taiwan;2. Institute of Biomedical Sciences, National Chung Hsing University, Taichung, 402, Taiwan;3. Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan;4. Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan;5. Department of Medicinal Botanicals and Health Applications, College of Biotechnology & Bioresources, Da-Yeh University;6. Department of Cosmetic Applications and Management, MacKay Junior College of Medicine, Nursing, and Management;7. Experimental Animal Center, Department of Molecular Biology and Cell Research, Chang Bing Show Chwan Memorial Hospital, Changhua, Taiwan |
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| 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 δ-tocotrienol (δT3) in B16 melanoma cells. Results showed that at 20 μM of δT3 significantly inhibited melanin formation and ROS generation. Treatment with δT3 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 δT3's inhibitory effect against melanin production. Specifically, δT3 treatment markedly induced the activation of extracellular signal-regulated kinases (ERK). The use of ERK activation inhibitor (PD98059) abrogated the δT3-mediated downregulation expression melanogenesis-related proteins and restored melanin production. Furthermore, siRNA targeting ERK effectively blocked the δT3-induced repression of tyrosinase and TYRP-1 expression. These results suggest that δT3'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 δT3's effect and the targeting of ERK signaling for treatment against melanogenesis. |
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| Keywords: | Tocotrienols Melanogenesis Tyrosinase MAPK ERK activation |
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