Carnosine inhibits KRas-mediated HCT-116 proliferation by affecting ATP and ROS production

Carnosine is a natural dipeptide that has aroused particular interest for its antioxidant, anti-aging and especially for its antiproliferative activity. In this study we demonstrated 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 50-100mM carnosine decreases ATP and ROS concentration and induces cell cycle arrest in G1 phase. These effects are related to decreased Erk1/2 phosphorylation and to an increase of p21waf1 protein. Our findings support the concept that carnosine could inhibit the HCT116 cell growth via its antioxidant activity and its ability to affect glycolysis.