Lee Yeji, Hyun Chang-Gu
Jeju Inside Agency and Cosmetic Science Center, Department of Chemistry and Cosmetics, Jeju National University, Jeju 63243, Korea.
Molecules. 2022 Apr 19;27(9):2613. doi: 10.3390/molecules27092613.
The objectives of this study were to investigate the melanogenetic potential of the psoralen derivatives 5-hydroxypsoralen, 5-methoxypsoralen, 8-hydroxypsoralen, 8-methoxypsoralen, and 5,8-dimethoxypsoralen in B16F10 melanoma cells. The results indicated that melanin production is significantly stimulated in B16F10 melanoma cells with 5-methoxypsoralen, 8-methoxypsoralen, and 5,8-dimethoxypsoralen, especially for 5-methoxypsoralen (bergapten), as reported previously. In addition, Western blot results showed that the protein levels of microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase-related protein-1 (TRP-1), and tyrosinase-related protein-2 (TRP-2) increase after bergapten treatment for the first time. The results also showed that bergapten promotes the phosphorylation of Akt at Ser 473 and glycogen synthase kinase-3β at Ser 9. Moreover, bergapten increased the content of β-catenin in the cell cytoplasm and nucleus by reducing the phosphorylated β-catenin (p-β-catenin) content. The results also indicated that bergapten regulates melanogenesis by upregulating the phosphorylation of p38 and JNK-mitogen-activated protein kinase. Taken together, these findings suggest that the regulation of melanogenesis by bergapten may be mediated by the β-catenin and MAPK signaling pathways and that bergapten might provide new insights into the pathogenesis of pigmented diseases.
本研究的目的是调查补骨脂素衍生物5-羟基补骨脂素、5-甲氧基补骨脂素、8-羟基补骨脂素、8-甲氧基补骨脂素和5,8-二甲氧基补骨脂素在B16F10黑色素瘤细胞中的黑素生成潜力。结果表明，如先前报道，5-甲氧基补骨脂素、8-甲氧基补骨脂素和5,8-二甲氧基补骨脂素可显著刺激B16F10黑色素瘤细胞产生黑色素，尤其是5-甲氧基补骨脂素（佛手柑内酯）。此外，蛋白质印迹结果首次显示，佛手柑内酯处理后，小眼相关转录因子（MITF）、酪氨酸酶、酪氨酸酶相关蛋白-1（TRP-1）和酪氨酸酶相关蛋白-2（TRP-2）的蛋白质水平增加。结果还表明，佛手柑内酯促进Akt在Ser 473位点和糖原合酶激酶-3β在Ser 9位点的磷酸化。此外，佛手柑内酯通过降低磷酸化β-连环蛋白（p-β-连环蛋白）的含量，增加了细胞质和细胞核中β-连环蛋白的含量。结果还表明，佛手柑内酯通过上调p38和JNK-丝裂原活化蛋白激酶的磷酸化来调节黑素生成。综上所述，这些发现表明，佛手柑内酯对黑素生成的调节可能由β-连环蛋白和MAPK信号通路介导，并且佛手柑内酯可能为色素沉着疾病的发病机制提供新的见解。
