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|Title:||Antiproliferative effects of oxygenated sterols: Positive correlation with binding affinities for the antiestrogen-binding sites||Authors:||Lin, L.
|Issue Date:||1991||Citation:||Lin, L., Hwang, P.L. (1991). Antiproliferative effects of oxygenated sterols: Positive correlation with binding affinities for the antiestrogen-binding sites. Biochimica et Biophysica Acta - Lipids and Lipid Metabolism 1082 (2) : 177-184. ScholarBank@NUS Repository. https://doi.org/10.1016/0005-2760(91)90192-K||Abstract:||Oxygenated derivatives of cholesterol have long been known to exhibit antiproliferative properties but the mechanism of this effect remains incompletely understood. Following up on a recent observation in our laboratory that certain oxysterols bind with high affinity to the microsomal antiestrogen-binding site, we attempted to determine if a relationship existed between the antiproliferative effect of oxysterols and their binding affinities for the antiestrogen-binding site. Using the human breast cancer cell line, MCF7, and 14 different compounds (4 nonsteroidal antiestrogens, 6 oxysterols with appreciable binding affinities for the antiestrogen-binding site, and 4 other sterols with little or no affinity for this site), we showed that for compounds which bound to the antiestrogen-binding site, there was a clear positive correlation between their relative cytotoxic potencies and their affinities for this binding site. Two sterols, namely 25-hydroxycholesterol and 20α-hydroxycholesterol, were exceptions to this general pattern, both clearly inhibited cell proliferation without having significant binding affinity for the antiestrogen-binding site. The same general order of antiproliferative potency of the oxysterols seen with MCF7 cells was also observed with the murine lymphoma cell line EL4. These findings suggest the possibility that the antiestrogen-binding site may be involved in mediating the antiproliferative effects of nonsteroidal antiestrogens and oxygenated sterols.||Source Title:||Biochimica et Biophysica Acta - Lipids and Lipid Metabolism||URI:||http://scholarbank.nus.edu.sg/handle/10635/107473||ISSN:||00052760||DOI:||10.1016/0005-2760(91)90192-K|
|Appears in Collections:||Staff Publications|
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