title: The Phytoestrogen Genistein Affects Breast Cancer Cells Treatment Depending on the ERα/ERβ Ratio.
abstract: Genistein (GEN) is a phytoestrogen found in soybeans. GEN exerts its functions through its interaction with the estrogen receptors (ER), ERα and ERβ, and we previously reported that the ERα/ERβ ratio is an important factor to consider in GEN-treated breast cancer cells. The aim of this study was to investigate the effects of GEN in breast cancer cells with different ERα/ERβ ratio: MCF-7 (high ratio), T47D (low ratio), and MCF-7 overexpressing ERβ (MCF7 + ERβ) treated with cisplatin (CDDP), paclitaxel (PTX) or tamoxifen (TAM). Cell viability, ROS production, autophagy, apoptosis, antioxidant enzymes protein levels, and cell cycle were analyzed. GEN treatment provoked an increase in cell viability in MCF-7 cells and in the antioxidant enzymes protein levels in combination with the cytotoxic agents, decreasing ROS production (CDDP + GEN and TAM+GEN) and autophagy (TAM + GEN) or apoptosis (CDDP + GEN and TAM + GEN). Moreover GEN treatment enhanced the cell cycle S phase entry in CDDP+GEN- and TAM + GEN-treated MCF-7 cells and, in the case of CDDP + GEN, increased the proportion of cells in the G2/M phase and decreased it in the subG0 /G1 phase. Otherwise, in the T47D and MCF7 + ERβ cells the combination of GEN with cytotoxic treatments did not cause significant changes in these parameters, even TAM + GEN-treated T47D cells showed less cell viability due to an increment in the autophagy. In conclusion, GEN consumption may be counterproductive in those patients receiving anticancer treatment with a high ERα/ERβ ratio diagnosed breast cancer and it could be harmless or even beneficial in those patients with a lower ERα/ERβ ratio breast cancer cells.
authors.affiliation: Grupo Multidisciplinar de Oncología Traslacional, Institut Universitari d'Investigació en Ciències de la Salut (IUNICS-IdISPa), Universitat de les Illes Balears, E07122 Palma de Mallorca, Illes Balears, Spain.|Ciber Fisiopatología Obesidad y Nutrición (CB06/03), Instituto de Salud Carlos III, Spain.
authors.forename: Daniel Gabriel
authors.initials: DG
authors.lastname: Pons
authors.affiliation: Grupo Multidisciplinar de Oncología Traslacional, Institut Universitari d'Investigació en Ciències de la Salut (IUNICS-IdISPa), Universitat de les Illes Balears, E07122 Palma de Mallorca, Illes Balears, Spain.|Ciber Fisiopatología Obesidad y Nutrición (CB06/03), Instituto de Salud Carlos III, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Nadal-Serrano
authors.affiliation: Grupo Multidisciplinar de Oncología Traslacional, Institut Universitari d'Investigació en Ciències de la Salut (IUNICS-IdISPa), Universitat de les Illes Balears, E07122 Palma de Mallorca, Illes Balears, Spain.|Ciber Fisiopatología Obesidad y Nutrición (CB06/03), Instituto de Salud Carlos III, Spain.
authors.forename: Margalida
authors.initials: M
authors.lastname: Torrens-Mas
authors.affiliation: Grupo Multidisciplinar de Oncología Traslacional, Institut Universitari d'Investigació en Ciències de la Salut (IUNICS-IdISPa), Universitat de les Illes Balears, E07122 Palma de Mallorca, Illes Balears, Spain.|Ciber Fisiopatología Obesidad y Nutrición (CB06/03), Instituto de Salud Carlos III, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Oliver
authors.affiliation: Grupo Multidisciplinar de Oncología Traslacional, Institut Universitari d'Investigació en Ciències de la Salut (IUNICS-IdISPa), Universitat de les Illes Balears, E07122 Palma de Mallorca, Illes Balears, Spain.|Ciber Fisiopatología Obesidad y Nutrición (CB06/03), Instituto de Salud Carlos III, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Roca
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism*; D005260:Female; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D061986:MCF-7 Cells; D048789:Phytoestrogens / Q000494:pharmacology*
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D048789:Phytoestrogens; D019833:Genistein
keywords: ANTICANCER TREATMENT; APOPTOSIS; AUTOPHAGY; BREAST CANCER; ERα/ERβ ratio; GENISTEIN; ROS PRODUCTION