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

Cláudia M Deus1,2, Teresa L Serafim1, Silvia Magalhães-Novais1

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

Archives of Toxicology
|July 1, 2016
PubMed

Insights

Resveratrol exhibits cytotoxicity in breast cancer cells by inhibiting mitochondrial respiration, a process dependent on sirtuin 1 (SIRT1). This study reveals SIRT1

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Research

Background:

  • Sirtuins are key regulators of cellular processes implicated in tumor development.
  • Resveratrol, a natural polyphenol, activates sirtuin 1 and 3 (SIRT1/3) and shows cytotoxicity in certain cancer types.
  • The precise mechanisms linking sirtuin activity, metabolic changes, and resveratrol's effects on breast cancer remain unclear.

Purpose of the Study:

  • To investigate the involvement of sirtuin 1 and 3 in resveratrol-induced cytotoxicity in breast cancer cells.
  • To determine if resveratrol induces cellular metabolic remodeling and differentiation.
  • To elucidate the role of SIRT1 in resveratrol's anti-cancer effects.

Main Methods:

  • Utilized the Extracellular Flux Analyzer to assess mitochondrial respiration in breast cancer cells.
  • Investigated the impact of resveratrol on sirtuin activity and breast cancer cell stemness markers.
  • Employed genetic or pharmacological modulators of SIRT1 to dissect its role.

Main Results:

  • Resveratrol was found to inhibit mitochondrial respiration in breast cancer cells.
  • Resveratrol's cytotoxic effects were modulated by SIRT1 and linked to mitochondrial complex I inhibition.
  • Resveratrol significantly reduced breast cancer cells expressing stemness markers in a SIRT1-dependent manner.

Conclusions:

  • Sirtuin 1 plays a critical role in mediating resveratrol's cytotoxic and differentiation-inducing effects on breast cancer cells.
  • Resveratrol impacts breast cancer cell metabolism, specifically mitochondrial respiration, via SIRT1.
  • Targeting SIRT1 may represent a therapeutic strategy for enhancing resveratrol's efficacy against breast cancer.
Keywords:
Breast cancerExtracellular flux analyzerMetabolismMitochondriaResveratrolSirtuinsToxicity

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