Stimulation of melanogenesis by scoparone in B16 melanoma cells
Stimulation of melanogenesis by scoparone in B16 melanoma cells
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DOI：
10.1111/j.1745-7254.2006.00435.x
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发表时间：
2006-11-01
影响因子：
8.2
通讯作者：
Park, Jin-woo
中科院分区：
文献类型：
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作者：
Yang, Jeong-yeh;Koo, Jeung-hyun;Park, Jin-woo
目的：研究香豆素衍生物对B16小鼠黑色素瘤细胞黑素合成的影响。方法：采用比色法测定黑色素含量和酪氨酸酶活性。采用逆转录聚合酶链反应（RT-PCR）和Western blot检测酪氨酸酶、酪氨酸酶相关蛋白-1（TRP-1）和酪氨酸酶相关蛋白-2（TRP-2）的表达。结果如下：在研究的香豆素衍生物中，滨蒿内酯（6，7-二甲氧基香豆素）是最有效的; 6-或7-甲氧基被认为是刺激黑素生成所必需的。滨蒿内酯可显著增加黑色素含量，且呈剂量依赖性;在有效浓度下无细胞毒性。滨蒿内酯增加酪氨酸酶的活性以及蛋白质和mRNA的表达。此外，滨蒿内酯处理后TRP-1和TRP-2的mRNA表达也增加。蛋白激酶A（PKA）抑制剂H-89完全抑制滨蒿内酯诱导的黑素生成和酪氨酸酶蛋白的增加。结论：这些结果表明，滨蒿内酯诱导的刺激黑素生成可能发生在转录水平的黑素生成相关酶通过PKA信号。
Aim: The effect of coumarin derivatives on melanogenesis was investigated in B16 murine melanoma cells. Methods: Melanin content and tyrosinase activity were analyzed spectrophotometrically. The expression of tyrosinase, tyrosinase-related protein-1 (TRP-1) and tyrosinase-related protein-2 (TRP-2) were measured either by reverse transcription-polymerase chain reaction (RT-PCR) or Western blot. Results: Among the coumarin derivatives studied, scoparone (6,7-dimethoxycoumarin) was the most potent; the 6- or 7-methoxy group was found to be essential for the stimulation of melanogenesis. The melanin content was greatly increased by scoparone in a dose-dependent manner; there was no cytotoxicity at the effective concentrations. Scoparone increased enzyme activity as well as protein and mRNA expression of tyrosinase. In addition, mRNA of TRP-1 and TRP-2 were also increased after treatment with scoparone. H-89, an inhibitor of protein kinase A (PKA), completely inhibited the scoparone-induced increase of melanogenesis and the tyrosinase protein. Conclusion: These results suggest that scoparone-induced stimulation of melanogenesis is likely to occur at the transcriptional level of melanogenesis-related enzymes through PKA signaling.