Treatment with the MEK Inhibitor U0126 Induces Increased Lactate Production in Prostate & Breast Cancer Cell Lines

Alessia Lodi¹, Sarah M. Woods¹, Robert M. Danforth¹, Sabrina M. Ronen¹

Malignant transformation often involves signaling pathway deregulation. Therefore, targeted inhibitors are under investigation as anticancer therapeutics. Here we investigated the metabolic consequences of treatment with a MAPK inhibitor in human prostate (PC3 and LNCaP) and breast (MCF7) cancer cells using proton and carbon MRS in vitro and in live cells, and gene expression analysis. Amongst other metabolic changes, the drug treatment consistently induced significantly increased production and intracellular accumulation of lactate. Concurrently, the overexpression of several glycolytic genes and the increased phosphorylation of Akt indicate that cross-talk between the MAPK and PI3K pathways induces an Akt-mediated enhanced glycolysis.