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

  • Molecular Toxicology
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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.

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Acknowledgments

This work was funded by FEDER funds through the Operational Programme Competitiveness Factors—COMPETE and national funds by FCT—Foundation for Science and Technology under research grants PTDC/DTP-FTO/1180/2012 and PTDC/AGR-ALI/108326/2008 and strategic project UID/NEU/04539/2013. Also supported by QREN project 4832 with reference CENTRO-07-ST24-FEDER-002008 financed through FEDER. CMD (SFRH/BD/100341/2014) and ACM (SFRH/BD/33892/2009) were supported by FCT PhD-fellowships and TLS (SFRH/BPD/75959/2011) and VAS (SFRH/BPD/31549/2006) are supported by FCT Pos-Doctoral fellowships.

Authors’ contribution

CMD performed most of the experiments, analyzed results, generated figures and wrote manuscript. TLS performed and design experiments. SMN, AV, ACM, VAS and SMC performed some of the experiments. PJO conceived and supervised the study, designed experiments and wrote part of the manuscript. All authors revised the final form of the manuscript.

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  1. CNC - Center for Neuroscience and Cell Biology, University of Coimbra, UC Biotech Building (Lot 8A), Biocant Park, 3060-197, Cantanhede, Portugal

    Cláudia M. Deus, Teresa L. Serafim, Silvia Magalhães-Novais, Andreia Vilaça, Ana C. Moreira, Vilma A. Sardão & Paulo J. Oliveira

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

    Cláudia M. Deus & Ana C. Moreira

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

    Susana M. Cardoso

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  1. Cláudia M. Deus
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Deus, C.M., Serafim, T.L., Magalhães-Novais, S. et al. Sirtuin 1-dependent resveratrol cytotoxicity and pro-differentiation activity on breast cancer cells. Arch Toxicol 91, 1261–1278 (2017). https://doi.org/10.1007/s00204-016-1784-x

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