The anticancer activity of genistein is increased in estrogen receptor beta 1-positive breast cancer cells

Abstract

BackgroundMost breast cancers are estrogen dependent and were sensitive to endocrine therapy, and genistein (GEN) shows strong affinity with human oestrogen receptor beta (ERβ).PurposeThe present study aimed to investigate the anticancer activity of GEN in breast cancer cell lines that constitutively expressing ERβ1 in vitro and in vivo.MethodsMCF-7/ERβ1 and MDA-MB-231/ERβ1 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 ERβ1-overexpressing cell lines. Studies in vivo were also performed to investigate the effects of dietary GEN on MCF-7/ERβ1 and MDA-MB-231/ERβ1 cells implanted mice.ResultsResults showed that compared to parental cells, GEN inhibited the proliferation ability of MCF-7/ERβ1 cells to a greater extent, especially at high concentrations. MDA-MB-231 cells were also inhibited by high doses of GEN, but the overexpressed ERβ1 did not enhance the anti-proliferative effect on MDA-MB-231 cells. ERβ1 arrested cells in G2/M phase, and GEN arrested cells in G0/G1, which led to a combinatorial effect on cell cycle blockade. Furthermore, ERβ1 increased the anti-tumour activity of dietary GEN in MCF-7/ERβ1 subcutaneous tumour models. Our data indicated that ERβ1 increased the anticancer efficacy of GEN in MCF-7 cells by affecting cell cycle transition.ConclusionAs a result, GEN could be a potential therapeutic agent for ERβ1-positive cancer.

The role of estrogen receptor beta in breast cancer

“…Many drug treatments have been shown to be mediated by ERβ and its isoforms [ 69 – 71 ]. ERβ can enhance the antiproliferative effects of raloxifene [ 72 , 73 ] and the sensitivity to anti-androgens in TNBC [ 74 ].…”

Epigenetic Activation of BRCA1 by Genistein In Vivo and Triple Negative Breast Cancer Cells Linked to Antagonism toward Aryl Hydrocarbon Receptor

“…The results of mechanistic studies in vitro show that the anti-tumorigenic activity of GEN in BC cells is largely attributable to the preferential induction of ERβ, which suppresses ERα signaling [25]. In ERα-positive MCF-7 cells, the overexpression of ERβ enhances the antiproliferative effects of GEN [26]. Other anti-tumorigenic effects of GEN in BC cells include inhibition of protein tyrosine kinase [e.g., epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR)] and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling [25].…”

New Insights into cytotoxic metabolites produced by Streptomyces griseus isolate KJ623766: Large scale production, structure elucidation and biological activities

“…Genistein was previously recognized to have some cellular actions including, glucose, lipid metabolism and other activities such as lipid peroxidation, inflammation, and fibrosis [28][29][30] as well as its antiviral activity against Herpes B Virus [31] and chondroprotective Effects against osteoarthritis [32].…”