Tamoxifen retards glycosphingolipid metabolism in human cancer cells

FEBS Lett. 1996 Sep 30;394(2):129-31. doi: 10.1016/0014-5793(96)00942-8.

Abstract

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 microM, 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Hormonal / pharmacology*
  • Chromatography, Thin Layer
  • Drug Resistance, Multiple
  • Glucosylceramides / metabolism*
  • Glucosyltransferases / antagonists & inhibitors*
  • Glycosphingolipids / metabolism*
  • Glycosylation / drug effects
  • Humans
  • KB Cells
  • Melanoma / metabolism
  • Molecular Structure
  • Neoplasms / metabolism*
  • Tamoxifen / analogs & derivatives
  • Tamoxifen / pharmacology*
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents, Hormonal
  • Glucosylceramides
  • Glycosphingolipids
  • Tamoxifen
  • afimoxifene
  • Glucosyltransferases
  • ceramide glucosyltransferase