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Tamoxifen retards glycosphingolipid metabolism in human cancer cells
Author(s) -
Cabot Myles C.,
Giuliano Armando E.,
Volner Alon,
Han Tie-Yan
Publication year - 1996
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(96)00942-8
Subject(s) - tamoxifen , lactosylceramide , glycosphingolipid , antiestrogen , chemistry , estrogen receptor , cancer cell , ceramide , pharmacology , endocrinology , cancer research , biochemistry , medicine , breast cancer , glycolipid , cancer , biology , apoptosis
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 [ 3 H]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.