Brown D A, Ren W Y, Khorlin A, Lesiak K, Conklin D, Watanabe K A, Seidman M M, George J
Codon Pharmaceuticals, Gaithersburg, Maryland 20877, USA.
J Invest Dermatol. 1998 Apr;110(4):428-37. doi: 10.1046/j.1523-1747.1998.00160.x.
We have found that several aliphatic and alicyclic diols induce melanogenesis in cultured S91 mouse melanoma cells and normal human epidermal melanocytes (NHEM). In addition, these compounds induce melanogenesis when applied to guinea pig skin, with transfer of melanin to keratinocytes and formation of "supranuclear caps," as occurs in naturally pigmented skin. The relative order of potency of some of these diols in NHEM is 5-norbornene-2,2-dimethanol > 3,3-dimethyl-1,2-butanediol > cis-1,2-cyclopentanediol > 2,3-dimethyl-2,3-butanediol > 1,2-propanediol. Following treatment with these diols or 3-isobutyl-1-methylxanthine, melanin and tyrosinase activity are increased within S91 cells and NHEM; however, for cultured NHEM, the largest increases of melanin and tyrosinase occur in an extracellular particulate fraction, shown by electron microscopy to consist almost entirely of stage III and IV melanosomes. These results indicate that cultured NHEM treated with diols export melanosomes in a fashion that is commensurate with natural melanogenic processes. In contrast, S91 mouse melanoma cells exhibit aberrant melanosomal trafficking, in accordance with the known defect in myosin-V mediated melanosomal transport. Both S91 cells and NHEM exhibit morphologic changes and growth arrest indicative of differentiation following treatment with diols. The diols described in this report are candidates for use as cosmeceutical tanning agents.
我们发现，几种脂肪族和脂环族二醇可在培养的S91小鼠黑素瘤细胞和正常人表皮黑素细胞（NHEM）中诱导黑素生成。此外，当将这些化合物应用于豚鼠皮肤时，它们会诱导黑素生成，黑素会转移至角质形成细胞并形成“核上帽”，就如同在天然色素沉着皮肤中发生的那样。这些二醇中的某些在NHEM中的效力相对顺序为：5-降冰片烯-2,2-二甲醇＞3,3-二甲基-1,2-丁二醇＞顺式-1,2-环戊二醇＞2,3-二甲基-2,3-丁二醇＞1,2-丙二醇。用这些二醇或3-异丁基-1-甲基黄嘌呤处理后，S91细胞和NHEM中的黑素和酪氨酸酶活性增加；然而，对于培养的NHEM，黑素和酪氨酸酶的最大增加发生在细胞外颗粒部分，电子显微镜显示该部分几乎完全由III期和IV期黑素小体组成。这些结果表明，用二醇处理的培养NHEM以与天然黑素生成过程相称的方式输出黑素小体。相比之下，S91小鼠黑素瘤细胞表现出异常的黑素小体运输，这与肌球蛋白-V介导的黑素小体运输中已知的缺陷一致。用二醇处理后，S91细胞和NHEM均表现出形态变化和生长停滞，这表明细胞发生了分化。本报告中描述的二醇有望用作药妆美黑剂。
