Chemistry and Biotechnology Examination Bureau, Korean Intellectual Property Office, Daejeon 302-701, Korea.
Int J Mol Med. 2010 Jul;26(1):101-6.
The present study was designed to assess the potential inhibitory activity of curcumin on the alpha-melanocyte stimulating hormone (alpha-MSH)-stimulated melanogenesis signal pathway in B16F10 melanoma cells. The molecular mechanism of curcumin-induced inhibitory activity on the alpha-MSH-stimulated melanogenesis signal pathway, including expression of melanogenesis-related proteins and activation of melanogenesis-regulating proteins, was examined in B16F10 cells. Curcumin suppressed the cellular melanin contents and the tyrosinase activity in alpha-MSH-stimulated B16F10 cells. In addition, the expression of melanogenesis-related proteins such as microphthalmia-associated transcription factor (MITF), tyrosinase, and tyrosinase-related protein 1 and 2 was suppressed by curcumin in the alpha-MSH-stimulated B16F10 cells. Notably, a melanogenesis-regulating signal such as mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) or phosphatidylinositol 3-kinase (PI3K)/Akt was activated by curcumin in the B16F10 cells treated with or without alpha-MSH. The suppressive activity of curcumin on alpha-MSH-induced melanogenesis was down-regulated by PD98059 and by LY294002. Our results suggest that the suppressive activity of curcumin on alpha-MSH-stimulated melanogenesis may involve the down-regulation of MITF and its downstream signal pathway through the activation of MEK/ERK or PI3K/Akt.
本研究旨在评估姜黄素对α-黑色素细胞刺激激素（α-MSH）刺激的黑色素生成信号通路的潜在抑制活性。在 B16F10 黑素瘤细胞中，研究了姜黄素诱导的对 α-MSH 刺激的黑色素生成信号通路的抑制活性的分子机制，包括黑色素生成相关蛋白的表达和黑色素生成调节蛋白的激活。姜黄素抑制了 α-MSH 刺激的 B16F10 细胞中的细胞黑色素含量和酪氨酸酶活性。此外，姜黄素还抑制了黑色素生成相关蛋白（如小眼畸形相关转录因子（MITF）、酪氨酸酶和酪氨酸酶相关蛋白 1 和 2）在 α-MSH 刺激的 B16F10 细胞中的表达。值得注意的是，在有或没有 α-MSH 处理的 B16F10 细胞中，姜黄素激活了黑色素生成调节信号，如丝裂原活化蛋白激酶激酶（MEK）/细胞外信号调节激酶（ERK）或磷脂酰肌醇 3-激酶（PI3K）/Akt。PD98059 和 LY294002 下调了姜黄素对 α-MSH 诱导的黑色素生成的抑制活性。我们的结果表明，姜黄素对 α-MSH 刺激的黑色素生成的抑制活性可能涉及通过 MEK/ERK 或 PI3K/Akt 的激活下调 MITF 及其下游信号通路。
