Sirtuin 1-dependent resveratrol cytotoxicity and pro-differentiation activity on breast cancer cells

send to a friend share this

Sirtuin 1-dependent resveratrol cytotoxicity and pro-differentiation activity on breast cancer cells

Wednesday, 03.08.2016


Cláudia M. Deus 1,2, Teresa L. Serafim 1, Silvia Magalhães-Novais 1, Andreia Vilaça 1, Ana C. Moreira 1,2, Vilma A. Sardão 1, Susana M. Cardoso 3 and Paulo J. Oliveira 1

1 CNC - Center for Neuroscience and Cell Biology, University of Coimbra, UC Biotech Building, Biocant Park, 3060-197 Cantanhede, Portugal

2 Department of Life Sciences, School of Sciences and Technology, University of Coimbra, 3004-517 Coimbra, Portugal

3 QOPNA – Department of Chemistry, University of Aveiro, Campus Universitário de Santiago, 3810-193 Aveiro, Portugal


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.

Journal: Archives of Toxicology – Springer

http://link.springer.com/article/10.1007%2Fs00204-016-1784-x