title: Genistein modulates proliferation and mitochondrial functionality in breast cancer cells depending on ERalpha/ERbeta ratio.
abstract: Breast cancer is the most common malignancy in women of developed countries. The aim of this study was to investigate whether genistein, a soy phytoestrogen, and 17β-estradiol (E2) could have effects on the cell cycle and mitochondrial function and dynamics. Three human breast cancer cell lines with different estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ) ratio were used: MCF-7 (high ERα/ERβ ratio), T47D (low ERα/ERβ ratio) and MDA-MB-231 (ER-negative). Cell proliferation, cell cycle, mitochondrial functionality, and mitochondrial dynamics parameters were analyzed. E2 and genistein treatment induced cell proliferation and apoptosis inhibition in MCF-7, but not in T47D and MDA-MB-231. Moreover, genistein treatment produced an up-regulation of ERβ and a rise in cytochrome c oxidase activity in T47D cells, decreasing the ATP synthase/cytochrome c oxidase ratio. Finally, genistein treatment produced a drop in mitochondrial dynamics only in MCF-7 cells. In summary, the beneficial effects of genistein consumption depend on the ERα/ERβ ratio in breast cells. Therefore, genistein treatment produces cell cycle arrest and an improvement of mitochondrial functionality in T47D cells with a low ERα/ERβ ratio, but not in MCF-7 (high ERα/ERβ ratio) and MDA-MB-231 (ER-negative) ones.
authors.affiliation: Grupo Multidisciplinar de Oncología Traslacional, Institut Universitari d'Investigació en Ciències de la Salut (IUNICS), Palma de Mallorca, Illes Balears, Spain; Ciber Fisiopatología Obesidad y Nutrición (CB06/03), Instituto Salud Carlos III, Madrid, Spain.
authors.forename: Daniel Gabriel
authors.initials: DG
authors.lastname: Pons
authors.forename: Mercedes
authors.initials: M
authors.lastname: Nadal-Serrano
authors.forename: M Mar
authors.initials: MM
authors.lastname: Blanquer-Rossello
authors.forename: Jorge
authors.initials: J
authors.lastname: Sastre-Serra
authors.forename: Jordi
authors.initials: J
authors.lastname: Oliver
authors.forename: Pilar
authors.initials: P
authors.lastname: Roca
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects*; D004958:Estradiol / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D019833:Genistein / Q000008:administration & dosage*; D006801:Humans; D061986:MCF-7 Cells; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004958:Estradiol; D019833:Genistein
keywords: 17β-ESTRADIOL; APOPTOSIS; CELL CYCLE; CELL PROLIFERATION; ESTROGEN RECEPTORS; GENISTEIN; MITOCHONDRIA