TAMOXIFEN RETARDS GLYCOSPHINGOLIPID METABOLISM IN HUMAN CANCER-CELLS

In this study we provide evidence that tamoxifen, the widely used brea st cancer drug, is a potent antagonist of glycolipid metabolism, When added to the medium of cultured multidrug resistant (MDR) KB-V-1 carci noma cells, tamoxifen, at 5.0 mu M, drastically lowered the levels of glucosylceramide (glc-cer), as evidenced by a reduction in glc-cer mas s, In a similar fashion, in cultured human melanoma cells grown with [ H-3]galactose, tamoxifen inhibited formation of glc-cer by 44%, and re tarded lactosylceramide and ganglioside formation by 50 and 35%, respe ctively. When glc-cer synthase of melanoma was assayed in cell-free in cubations, the inclusion of tamoxifen, at a 1:10 molar ratio with cera mide, inhibited glc-cer synthesis by 50%. These results clearly reveal a new action of tamoxifen and thereby pose intriguing questions regar ding mechanisms of action in the realm of estrogen receptor-independen t modalities, including effects on MDR.