Carnosine inhibits KRAS-mediated HCT116 proliferation by affecting ATP and ROS production

Cancer Lett. 2012 Feb 28;315(2):122-8. doi: 10.1016/j.canlet.2011.07.021. Epub 2011 Aug 5.

Abstract

Carnosine is a natural dipeptide that has generated particular interest for its antioxidant, anti-aging and especially for its antiproliferative properties. In this study, we demonstrate that carnosine inhibits the proliferation of human HCT116 colon cancer cells. In this cell line, the activating KRAS mutation induces mitochondrial ROS, the signaling molecules for cell proliferation. We observed that 50-100 mM carnosine decreases ATP and ROS concentration and induces cell cycle arrest in G1 phase. In HCT116 cells these effects are related to decreased ERK1/2 phosphorylation and increased p21waf1 protein. Our findings support the concept that carnosine could inhibit HCT116 cell growth via its antioxidant activity and its ability to affect glycolysis.

MeSH terms

  • Adenosine Triphosphate / metabolism*
  • Antioxidants / pharmacology*
  • Blotting, Western
  • Carnosine / pharmacology*
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Flow Cytometry
  • Glycolysis / drug effects
  • HCT116 Cells
  • Humans
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins p21(ras)
  • Reactive Oxygen Species / metabolism*
  • ras Proteins / metabolism*

Substances

  • Antioxidants
  • KRAS protein, human
  • Proto-Oncogene Proteins
  • Reactive Oxygen Species
  • Carnosine
  • Adenosine Triphosphate
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins