title: Genistein modulates oxidative stress in breast cancer cell lines according to ERα/ERβ ratio: effects on mitochondrial functionality, sirtuins, uncoupling protein 2 and antioxidant enzymes.
abstract: Genistein is a biologically active isoflavone with estrogenic activity and can be found in a variety of soy products. This natural compound displays a wide array of biological activities, but it is best known for its ability to inhibit cancer progression, especially for hormone-related ones such as breast cancer. Genistein has been shown to bind both the estrogen receptor alpha (ERα) and the estrogen receptor beta (ERβ), although it has a higher affinity for the ERβ. The ERα/ERβ ratio is a prognostic marker for breast tumors, and ERβ expression could indicate the presence of tumors more benign in state, whereas ERα indicates malignant tumors. The objective of the present study was to investigate the effects of genistein on oxidative stress and mitochondrial functionality through its interaction with the estrogen receptor in breast cancer cell lines with different ERα/ERβ ratios. The lower ERα/ERβ ratio T47D cell line showed lower oxidative stress and greater mitochondrial functionality, along with an up-regulation of uncoupling protein 2 and sirtuins. On the other hand, genistein-treated MCF-7 cell line, with the highest ERα/ERβ ratio, reported no changes for the control situation. On the whole, our results show different genistein effects depending on ERα/ERβ ratio for oxidative stress regulation, mitochondrial functionality, and modulation of UCPs, antioxidant enzymes and sirtuins in breast cancer cell lines. Effects of genistein on oxidative stress and mitochondria could be due at least in part, to a higher ERβ presence, but could also be due to up-regulation of ERβ caused by the genistein treatment.
authors.affiliation: Grupo multidisciplinar de Oncología Traslacional, Institut Universitari d'Investigació en Ciències de la Salut IUNICS, Universitat de les Illes Balears, E07122 Palma de Mallorca, Illes Balears, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Nadal-Serrano
authors.forename: Daniel Gabriel
authors.initials: DG
authors.lastname: Pons
authors.forename: Jorge
authors.initials: J
authors.lastname: Sastre-Serra
authors.forename: M del Mar
authors.initials: Mdel M
authors.lastname: Blanquer-Rosselló
authors.forename: Pilar
authors.initials: P
authors.lastname: Roca
authors.forename: Jordi
authors.initials: J
authors.lastname: Oliver
mesh_terms: D000975:Antioxidants / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism*; D005260:Female; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D061986:MCF-7 Cells; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism*; D000071246:Uncoupling Protein 2
chemical_list: D000975:Antioxidants; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D007473:Ion Channels; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; C000604389:UCP2 protein, human; D000071246:Uncoupling Protein 2; D019833:Genistein; D037761:Sirtuins
keywords: 2′,7′-dichlorofluorescein diacetate; 4-HNE; 4-hydroxy-2-nonenal; Breast cancer; CAT; DCFDA; ERα; ERα/ERβ ratio; ERβ; GEN; Genistein; Mitochondria; MnSOD; NAO; Nonyl Acridine Orange; OXPHOS; Oxidative stress; ROS; SIRT; TMRM; UCP; catalase; estrogen receptor alpha; estrogen receptor beta; genistein; manganese superoxide dismutase; mitochondrial membrane potential; oxidative phosphorylation; reactive oxygen species; sirtuin; tetramethylrhodamine methyl ester; uncoupling protein; Δψm