Effect of estrogen receptor β agonists on proliferation and gene expression of ovarian cancer cells

Abstract

BackgroundEstrogen receptor (ER) β has been suggested to affect ovarian carcinogenesis. We examined the effects of four ERβ agonists on proliferation and gene expression of two ovarian cancer cell lines.MethodsOVCAR-3 and OAW-42 ovarian cancer cells were treated with the ERβ agonists ERB-041, WAY200070, Liquiritigenin and 3β-Adiol and cell growth was measured by means of the Cell Titer Blue Assay (Promega). ERβ expression was knocked down by transfection with specific siRNA. Additionally, transcriptome analyses were performed by means of Affymetrix GeneChip arrays. To confirm the results of DNA microarray analysis, Western blot experiments were performed.ResultsAll ERβ agonists tested significantly decreased proliferation of OVCAR-3 and OAW-42 cells at a concentration of 10 nM. Maximum antiproliferative effects were induced by flavonoid Liquiritigenin, which inhibited growth of OVCAR-3 cells by 31.2% after 5 days of treatment, and ERB-041 suppressing proliferation of the same cell line by 29.1%. In OAW-42 cells, maximum effects were observed after treatment with the ERβ agonist WAY200070, inhibiting cell growth by 26.8%, whereas ERB-041 decreased proliferation by 24.4%. In turn, knockdown of ERβ with specific siRNA increased cell growth of OAW-42 cells about 1.9-fold. Transcriptome analyses revealed a set of genes regulated by ERβ agonists including ND6, LCN1 and PTCH2, providing possible molecular mechanisms underlying the observed antiproliferative effects.ConclusionIn conclusion, the observed growth-inhibitory effects of all ERβ agonists on ovarian cancer cell lines in vitro encourage further studies to test their possible use in the clinical setting.

Indole Derivative Interacts with Estrogen Receptor Beta and Inhibits Human Ovarian Cancer Cell Growth

“…We then focused on exploring the effect of compound 3 on the histone acetylation and gene expression in IGROV1. At 6 h of treatment, compound 3 induces an increase of acetylated H4 isoforms ( Figure 5 ) and a downregulation of MYC and CCND1 genes ( Figure 6 a), acting as an ERβ agonist, in accordance with other findings on other agonists [ 30 , 31 ].…”

Targeting estrogen receptor beta (ERβ) for treatment of ovarian cancer: importance of KDM6B and SIRT1 for ERβ expression and functionality

“…It has previously been reported that ERβ mediates ovarian cancer cell growth repression by decreasing the cellular content of, among others, retinoblastoma, phospho-AKT, cyclin D1, and A2 as well as upregulating the cyclin-dependent kinase inhibitor p21 13 , 14 , 26 , 27 . In this report we have focused on other aspects of ERβ function and activity as a ligand-activated transcription factor and growth inhibitor of tumor cells.…”

Estrogen receptor β is associated with expression of cancer associated genes and survival in ovarian cancer

“…In vitro, we showed reduced proliferation and migration of ovarian cancer cells after overexpression of ERβ as well as increased rates of apoptosis [ 12 ]. Moreover, we found a significant growth-inhibition of ovarian cancer cells by treatment with specific ERβ-agonists [ 13 ]. Thus, these data support the tumor suppressive role of ERβ in ovarian cancer.…”

“…Previous studies clearly suggest a tumor suppressive role of ERβ in ovarian cancer as it has been shown for breast or prostate cancer [ 9 – 11 ]. Our group demonstrated that ERβ reduces proliferation and migration, but activates apoptosis of ovarian cancer cells [ 12 ] and that specific ERβ-agonists significantly inhibit growth of different ovarian cancer cell lines [ 13 ]. Furthermore, our results from a phenotype-genotype association study suggested that the single nucleotide polymorphism rs3020449 in the promoter region of ESR2 gene might affect progression of ovarian cancer [ 14 ].…”