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

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.

► Carnosine is a free radical scavenger.
► Carnosine inhibits the colon cancer cells growth via its antioxidant activity.
► Carnosine reduces ROS levels as well as the phosphorylation level of Erk1/2.
► It induces G1 arrest in colon cancer cells by inhibiting the G1–S phase transition.
► The anti-proliferative effect is related to its ability to affect glycolysis.