Thody A J, Oliver I, Sherbet G V
Department of Dermatology, University of Newcastle upon Tyne, U.K.
Eur J Cancer Clin Oncol. 1988 Dec;24(12):1879-84. doi: 10.1016/0277-5379(88)90101-0.
The melanocytotoxic effects of 4-hydroxyanisole (4-OHA) are thought to depend upon its conversion to toxic oxidation products by the enzyme tyrosinase. In this study, the cytotoxicity of 4-OHA was examined in different B16 melanoma cell lines that show varying levels of tyrosinase and after stimulation by melanocyte-stimulating hormone (MSH) and all-trans-retinoic acid (RA). 4-OHA decreased cell survival of three melanotic and one amelanotic cell line in culture, but the effect was unrelated to their tyrosinase activity or the subcellular localization of the enzyme. Although stimulation of tyrosinase activity with RA enhanced the cytotoxicity of 4-OHA, no similar enhancement occurred with alpha-MSH. It appears that there is no relationship between the cytotoxic effects of 4-OHA and intracellular tyrosinase and the enhancement of its cytotoxicity by RA may well be related to the antiproliferative effects of the retinoid.
4-羟基茴香醚（4-OHA）的黑素细胞毒性作用被认为取决于它被酪氨酸酶转化为有毒的氧化产物。在本研究中，检测了4-OHA在不同B16黑色素瘤细胞系中的细胞毒性，这些细胞系显示出不同水平的酪氨酸酶，并且在受到促黑素细胞激素（MSH）和全反式维甲酸（RA）刺激之后。4-OHA降低了培养中的三种黑素瘤细胞系和一种无黑素细胞系的细胞存活率，但该效应与它们的酪氨酸酶活性或该酶的亚细胞定位无关。虽然用RA刺激酪氨酸酶活性增强了4-OHA的细胞毒性，但α-MSH未产生类似增强作用。看来4-OHA的细胞毒性作用与细胞内酪氨酸酶之间没有关系，并且RA对其细胞毒性的增强很可能与类视黄醇的抗增殖作用有关。
