AI Article Synopsis
- Tamoxifen, a common breast cancer treatment, significantly disrupts glycolipid metabolism in cancer cells by lowering glucosylceramide levels.
- In studies on MDR KB-V-1 carcinoma cells and human melanoma cells, tamoxifen inhibited the formation of glucosylceramide and related molecules, with reductions of 44% to 50%.
- These findings suggest that tamoxifen may have effects unrelated to its estrogen receptor inhibition, highlighting potential new therapeutic mechanisms, especially in multidrug-resistant cancers.
Article 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.
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| http://dx.doi.org/10.1016/0014-5793(96)00942-8 | DOI Listing |
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