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

作者：Ng Lean Teik; Lin Liang Tzung; Chen Chiu Lan; Chen Hsiu Wen; Wu Shu Jing; Lin Chun Ching^*

来源：Phytomedicine, 2014, 21(7): 978-983.

DOI：10.1016/j.phymed.2014.03.003

• Tocotrienols
• Melanogenesis
• Tyrosinase
• MAPK
• ERK activation

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 delta-tocotrienol (delta T3) in B16 melanoma cells. Results showed that at 20 mu M of delta T3 significantly inhibited melanin formation and ROS generation. Treatment with delta 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 delta T3%26apos;s inhibitory effect against melanin production. Specifically, delta T3 treatment markedly induced the activation of extracellular signal-regulated kinases (ERR). The use of ERR activation inhibitor (PD98059) abrogated the delta T3-mediated downregulation expression melanogenesis-related proteins and restored melanin production. Furthermore, siRNA targeting ERK effectively blocked the delta T3-induced repression of tyrosinase and TYRP-1 expression. These results suggest that delta T3%26apos;s inhibitory effect against melanogenesis is mediated by the activation of ERR signaling, thereby resulting in downstream repression of melanogenesis-related proteins and the subsequent melanin production. These data provide insight to delta T3%26apos;s effect and the targeting of ERR signaling for treatment against melanogenesis.

• 出版日期2014-6-15