Melanoma cytotoxicity of buthionine sulfoximine (BSO) alone and in combination with 3,4-dihydroxybenzylamine and melphalan.
Melanoma cytotoxicity of buthionine sulfoximine (BSO) alone and in combination with 3,4-dihydroxybenzylamine and melphalan.
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DOI：
10.1111/1523-1747.ep12616629
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发表时间：
1992-09
期刊：
影响因子：
--
通讯作者：
J. Prezioso;G. Fitzgerald;M. Wick
中科院分区：
文献类型：
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作者：
J. Prezioso;G. Fitzgerald;M. Wick
Buthionine sulfoximine （BSO）是一种特异性的谷胱甘肽合成抑制剂，在不同的肿瘤细胞系中表现出不同的生长抑制活性，对黑色素瘤来源的细胞系具有高度的抑制活性。BSO生长抑制作用与细胞谷胱甘肽过氧化物酶活性之间存在相关性。相反，对BSO的反应与细胞酪氨酸酶、γ -谷氨酰半胱氨酸合成酶、谷胱甘肽转移酶、γ -谷氨酰转肽酶或谷胱甘肽还原酶活性之间没有相关性。BSO增强3,4-二羟基苯胺（3,4- dhba）（4倍）和美法兰（3倍）的体外细胞毒活性，这是通过抑制人类黑色素瘤细胞DNA合成来确定的，这种增强取决于暴露于药物的持续时间。BSO在B16黑素瘤小鼠体内显示出抗肿瘤活性，使生存期延长29%，与3,4- dhba联合使用，与单独使用3,4- dhba相比，寿命略有延长（48%对38%）。然而，BSO和melphalan联合使用，与单独使用melphalan相比，B16黑色素瘤小鼠的寿命延长了170%（80%）。这些研究证明了BSO在体内具有独特的抗黑色素瘤活性。
Buthionine sulfoximine (BSO), a specific inhibitor of glutathione synthesis, showed variable growth-inhibitory activity in different tumor cell lines with a high degree of inhibitory activity against melanoma-derived cell lines. A correlation between BSO growth-inhibitory effects and cellular glutathione peroxidase activity was observed. In contrast, no correlation was demonstrated between the response to BSO and cellular tyrosinase, gamma-glutamylcysteine synthetase, glutathione transferase, gamma-glutamyl transpeptidase, or glutathione reductase activities. BSO enhanced 3,4-dihydroxybenzylamine (3,4-DHBA) (fourfold) and melphalan (threefold) in vitro cytotoxic activity as determined by inhibition of DNA synthesis in human melanoma cells and this enhancement was dependent on the duration of exposure to drug. BSO demonstrated in vivo antitumor activity in B16 melanoma-bearing mice prolonging survival by 29% and in combination with 3,4-DHBA resulted in a slight (48% versus 38%) increase in life span as compared to 3,4-DHBA alone. The combination of BSO and melphalan, however, increased the life span of B16 melanoma-bearing mice by 170%, as compared to melphalan alone (80%). These studies demonstrate a unique in vivo antimelanoma activity of BSO.