title: Sirtuin 1-dependent resveratrol cytotoxicity and pro-differentiation activity on breast cancer cells.
abstract: Sirtuins regulate several processes associated with tumor development. Resveratrol was shown to stimulate sirtuin 1 and 3 (SIRT1/3) activities and to result in cytotoxicity for some tumor types. The relationship between modulation of sirtuin activities, cellular metabolic remodeling and resveratrol cytotoxicity mechanism on breast cancer cells is still an open question. Here, we evaluated whether sirtuin 1 and 3 are involved in resveratrol toxicity and whether resveratrol leads to a metabolic remodeling and cell differentiation. Results using the Extracellular Flux Analyzer indicated that resveratrol inhibits mitochondrial respiration in breast cancer cells. We also demonstrated here for the first time that resveratrol cytotoxic effects on breast cancer cells were modulated by SIRT1 and also involved mitochondrial complex I inhibition. Importantly, we also demonstrated that resveratrol reduced the pool of breast cancer cells with stemness markers through a SIRT1-dependent mechanism. Our data highlights the role of SIRT1 in regulating resveratrol induced differentiation and/or toxicity in breast cancer cells.
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, UC Biotech Building (Lot 8A), Biocant Park, 3060-197, Cantanhede, Portugal.|Department of Life Sciences, School of Sciences and Technology, University of Coimbra, 3004-517, Coimbra, Portugal.
authors.forename: Cláudia M
authors.initials: CM
authors.lastname: Deus
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, UC Biotech Building (Lot 8A), Biocant Park, 3060-197, Cantanhede, Portugal.
authors.forename: Teresa L
authors.initials: TL
authors.lastname: Serafim
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, UC Biotech Building (Lot 8A), Biocant Park, 3060-197, Cantanhede, Portugal.
authors.forename: Silvia
authors.initials: S
authors.lastname: Magalhães-Novais
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, UC Biotech Building (Lot 8A), Biocant Park, 3060-197, Cantanhede, Portugal.
authors.forename: Andreia
authors.initials: A
authors.lastname: Vilaça
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, UC Biotech Building (Lot 8A), Biocant Park, 3060-197, Cantanhede, Portugal.|Department of Life Sciences, School of Sciences and Technology, University of Coimbra, 3004-517, Coimbra, Portugal.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Moreira
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, UC Biotech Building (Lot 8A), Biocant Park, 3060-197, Cantanhede, Portugal.
authors.forename: Vilma A
authors.initials: VA
authors.lastname: Sardão
authors.affiliation: QOPNA - Department of Chemistry, University of Aveiro, Campus Universitário de Santiago, 3810-193, Aveiro, Portugal.
authors.forename: Susana M
authors.initials: SM
authors.lastname: Cardoso
authors.affiliation: CNC - Center for Neuroscience and Cell Biology, University of Coimbra, UC Biotech Building (Lot 8A), Biocant Park, 3060-197, Cantanhede, Portugal. pauloliv@cnc.uc.pt.
authors.forename: Paulo J
authors.initials: PJ
authors.lastname: Oliveira
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D019069:Cell Respiration / Q000187:drug effects; D042967:Electron Transport Complex I / Q000037:antagonists & inhibitors / Q000378:metabolism; D005260:Female; D006801:Humans; D061986:MCF-7 Cells / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D017208:Rats, Wistar; D000077185:Resveratrol; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*; D056566:Sirtuin 3 / Q000235:genetics / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D013267:Stilbenes; C447939:SIRT1 protein, human; C466093:SIRT3 protein, human; D056564:Sirtuin 1; D056566:Sirtuin 3; D042967:Electron Transport Complex I; D000077185:Resveratrol
keywords: Breast cancer; Extracellular flux analyzer; Metabolism; Mitochondria; Resveratrol; Sirtuins; Toxicity