The anticancer activity of genistein is increased in estrogen receptor beta I-positive breast cancer cells

Background: Most breast cancers are estrogen dependent and were sensitive to endocrine therapy, and genistein (GEN) shows strong affinity with human oestrogen receptor beta (ER beta). Purpose: The present study aimed to investigate the anticancer activity of GEN in breast cancer cell lines that constitutively expressing ER beta 1 in vitro and in vivo. Methods: MCF-7/ER beta 1 and MDA-MB-231/ER beta 1 cell sub-lines were established through lentiviral infection. Then, cells were treated with increasing concentrations of GEN (10(-6)mol/l, 10(-5)mol/l and 10(-4)mol/l) for 48 h, and cell proliferation, cell cycle analyses were performed to investigate different biological characteristics of ER beta 1-overexpressing cell lines. Studies in vivo were also performed to investigate the effects of dietary GEN on MCF-7/ER beta 1 and MDA-MB-231/ER beta 1 cells implanted mice. Results: Results showed that compared to parental cells, GEN inhibited the proliferation ability of MCF-7/ER beta 1 cells to a greater extent, especially at high concentrations. MDA-MB-231 cells were also inhibited by high doses of GEN, but the overexpressed ER beta 1 did not enhance the anti-proliferative effect on MDA-MB-231 cells. ER beta 1 arrested cells in G2/M phase, and GEN arrested cells in GO/G1, which led to a combinatorial effect on cell cycle blockade. Furthermore, ER beta 1 increased the anti-tumour activity of dietary GIN in MCF-7/ER beta 1 subcutaneous tumour models. Our data indicated that ER beta 1 increased the anticancer efficacy of GEN in MCF-7 cells by affecting cell cycle transition. Conclusion: As a result, GEN could be a potential therapeutic agent for ER beta 1-positive cancer.