Effects of tyrosinase activity on the cytotoxicity of 3,4-dihydroxybenzylamine and buthionine sulfoximine in human melanoma cells.
Effects of tyrosinase activity on the cytotoxicity of 3,4-dihydroxybenzylamine and buthionine sulfoximine in human melanoma cells.
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酪氨酸酶活性对人黑色素瘤细胞中 3,4-二羟基苄胺和丁硫氨酸亚磺酰亚胺细胞毒性的影响。
DOI：
10.1111/j.1600-0749.1990.tb00322.x
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发表时间：
1990
期刊：
影响因子：
--
通讯作者：
Wick,MM
中科院分区：
文献类型：
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作者：
Prezioso,JA;Fitzgerald,GB;Wick,MM
黑色素瘤特异性含二羟基苯的抗肿瘤剂的基本原理部分基于酪氨酸酶将这些前药氧化成毒性中间体的能力。原位酪氨酸酶活性被证明受到色素性黑素瘤细胞中细胞密度和铺板时间的影响。发现完全抑制酪氨酸酶活性且具有最小细胞毒性的苯基硫脲可阻断抗肿瘤多巴胺类似物3，4-二羟基苄胺（3，4-DHBA）（NSC 263475）的生长抑制活性。还发现抗氧化剂二硫代巴比妥可抑制酪氨酸酶活性，并阻断3，4-DHBA在色素性黑色素瘤细胞系中的生长抑制作用。丁硫酰亚胺亚砜（BSO）显示出对黑色素瘤细胞具有细胞毒性，其生长抑制作用似乎与酪氨酸酶水平相关。此外，BSO显示出增强3，4-DHBA对边缘着色的人黑素瘤细胞系的生长抑制作用。
The rationale for melanoma specific dihydroxybenzene containing antitumor agents is based in part upon the ability of the enzyme tyrosinase to oxidize these pro drugs to toxic intermediates. In situ tyrosinase activity was demonstrated to be affected by both cell density and time from plating in pigmented melanoma cells. Phenylthiourea, which completely inhibited tyrosinase activity with minimal cytotoxicity was found to block the growth inhibitory activity of the antitumor dopamine analog 3,4‐dihydroxybenzylamine (3,4‐DHBA) (NSC 263475). The antioxidant dithioerythritol was also found to inhibit tyrosinase activity and to block the growth inhibitory effects of 3,4‐DHBA in pigmented melanoma cell lines. Buthionine sulfoximine (BSO) was shown to be cytotoxic to melanoma cells and its growth inhibitory effects appears to correlate with tyrosinase levels. Furthermore, BSO was shown to potentiate the growth inhibitory effects of 3,4‐DHBA on marginally pigmented human melanoma cell lines.