Tamoxifen retards glycosphingolipid metabolism in human cancer cells

FEBS Letters

Han, Tie-Yan¹  Cabot, Myles C.¹  Volner, Alon¹  Giuliano, Armando E.¹ 

[1] John Wayne Cancer Institute at Saint John's Hospital and Health Center, 2200 Santa Monica Blvd., Santa Monica, CA 90404, USA

关键词: Tamoxifen;    Glycosphingolipids;    Glucosylceramide;    Multidrug resistance;    Cancer;    MDR;    multidrug resistance;    glc-cer;    glucosylceramide;    FBS;    fetal bovine serum;    TLC;    thin-layer chromatography;   

DOI  :  10.1016/0014-5793(96)00942-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 μM, 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 [³H]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.

【 授权许可】

Unknown