Monchusi, B.Ntwasa, M.2017-10-182017-10-182017-08Monchusi, B. and Ntwasa, M. 2017. Methyl pyruvate protects a normal lung fibroblast cell line from irinotecan-induced cell death: Potential use as adjunctive to chemotherapy. PLOS ONE 12(8), Article number e01827891932-6203 (Online)http://hdl.handle.net/10539/23271The Warburg Effect, characterized by increased rate of glycolysis even under normoxic conditions, is one of the hallmarks of cancer. Relatively lower oxidative phosphorylation (OXPHOS) is also a characteristic feature in cancer cells. We hypothesized that interference with this phenomenon, by introducing exogenous pyruvate, would upset this cancer phenotype and boost the energy requirements of normal cells. We find that methyl pyruvate protects irinotecan-treated normal lung fibroblast cell line (MRC-5) probably by turning off the p53/p21 axis of the apoptotic pathways. When the MRC-5 fibroblasts recover in drug-free medium, the intrinsic apoptotic pathway is also turned off and the cells survive with no discernible exponential growth during the observation period. In contrast, the mere introduction of exogenous pyruvate kills the lung cancer cell line (A549). Although, functional p53 is important in the drug-induced cancer cell death, it is probably not essential because cancer cell lines with mutated p53 also die albeit less efficiently. We conclude that methyl pyruvate may preferentially kill cancer cells and protect normal cells during chemotherapy.en© 2017 Monchusi, Ntwasa. This is an open access article distributed under the terms of the Creative Commons Attribution License.GlycolysisOxidative phosphorylationCancerExogenous pyruvateMethyl pyruvateExogenous pyruvateFibroblast cellChemotherapyMODULATE EXPRESSIONAEROBIC GLYCOLYSISBINDING-PROTEINETHYL PYRUVATEP53CYCLERESPIRATIONMETABOLISMSENESCENCEMethyl pyruvate protects a normal lung fibroblast cell line from irinotecan-induced cell death: Potential use as adjunctive to chemotherapyArticle