Tamoxifen retards glycosphingolipid metabolism in human cancer cells
Tamoxifen retards glycosphingolipid metabolism in human cancer cells
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DOI：
10.1016/0014-5793(96)00942-8
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发表时间：
1996-09-30
期刊：
影响因子：
3.5
通讯作者：
Han, TY
中科院分区：
文献类型：
--
作者：
Cabot, MC;Giuliano, AE;Han, TY
在这项研究中，我们提供了广泛使用的乳腺癌药物他莫昔芬是糖脂代谢的有效拮抗剂的证据。当将5.0 μ M的他莫昔芬添加到培养的多药耐药（MDR）KB-V-1癌细胞的培养基中时，显著降低了葡萄糖神经酰胺（glc-cer）的水平，如glc-cer质量的减少所证明的。以类似的方式，在与[H-3]半乳糖一起生长的培养的人黑素瘤细胞中，他莫昔芬抑制glc-cer的形成达44%，并分别延迟乳糖神经酰胺和神经节苷脂的形成达50%和35%。当黑色素瘤的glc-cer合成酶在无细胞培养中进行测定时，包含他莫昔芬，与神经酰胺的摩尔比为1：10，抑制glc-cer合成50%。这些结果清楚地揭示了他莫昔芬的新作用，从而提出了关于雌激素受体非依赖性模式领域的作用机制的有趣问题，包括对MDR的影响。
In this study we provide evidence that tamoxifen, the widely used breast cancer drug, is a potent antagonist of glycolipid metabolism, When added to the medium of cultured multidrug resistant (MDR) KB-V-1 carcinoma cells, tamoxifen, at 5.0 mu M, drastically lowered the levels of glucosylceramide (glc-cer), as evidenced by a reduction in glc-cer mass, In a similar fashion, in cultured human melanoma cells grown with [H-3]galactose, tamoxifen inhibited formation of glc-cer by 44%, and retarded lactosylceramide and ganglioside formation by 50 and 35%, respectively. When glc-cer synthase of melanoma was assayed in cell-free incubations, the inclusion of tamoxifen, at a 1:10 molar ratio with ceramide, inhibited glc-cer synthesis by 50%. These results clearly reveal a new action of tamoxifen and thereby pose intriguing questions regarding mechanisms of action in the realm of estrogen receptor-independent modalities, including effects on MDR.