Proteomic response to cytotoxicity of methylglyoxall

Tumor glycolysis is a target for cancer chemotherapy. Methylglyoxal (MG) is a reactive metabolite formed mainly as a by-product in anaerobic glycolysis, metabolized by glyoxalase 1 (Glo1) of the glyoxalase system. MG is increased to cytotoxic levels by clinical anticancer drugs, contributing to their mechanism of action. We investigated the role of the proteomic response to MG in mediating cytotoxicity. The proteomic response to MG-induced cytotoxicity was explored by high mass resolution proteomics of cytoplasmic and other subcellular protein extracts. MG induced decrease of mitochondrial and spliceosomal proteins. Spliceosomal proteins were targets of MG modification. We conclude that MG-mediated cytotoxicity targets the spliceosome.