OBJECTIVETo investigate the effect of xy2004, a centchroman derivative, on the proliferation of MCF-7 cells and the mechanisms.

METHODSThe effects of xy2004 on MCF-7 cell proliferation and apoptosis were evaluated with MTT assay and flow cytometry, respectively. The expressions of the apoptosis-related proteins were examined with Western blotting. Competitive estrogen-receptor binding assay was used to investigate the affinity of xy2004 to estrogen receptors (ER).

RESULTSxy2004 induced proliferation of MCF-7 cells at low concentrations but inhibited cell proliferation at high concentrations. The application of tamoxifen inhibited xy2004-induced proliferation of MCF-7 cells. The relative binding affinity of xy9906 to ERα and ERβ, presented as the IC50 value, was 7.38 × 10⁻³ mol/L and 4.12 × 10⁻⁷ mol/L, respectively. Treatment of MCF-7 cells with high-concentration xy2004 reduced the cellular expression of Bcl-2 protein and increased Bax protein expression.

CONCLUSIONAt low concentrations, xy2004 directly stimulates the proliferation of MCF -7 cells through ligand-receptor binding, and at high concentrations, it inhibits the cell proliferation by regulating the expression levels of the apoptosis-related proteins.

Apoptosis ; Breast Neoplasms ; pathology ; Cell Proliferation ; Centchroman ; pharmacology ; Estrogen Receptor alpha ; metabolism ; Estrogen Receptor beta ; metabolism ; Humans ; MCF-7 Cells ; drug effects ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Tamoxifen ; bcl-2-Associated X Protein ; metabolism