Methyl pyruvate protects a normal lung fibroblast cell line from irinotecan-induced cell death: Potential use as adjunctive to chemotherapy

• Published in: PloS one Vol. 12; no. 8; p. e0182789
• Main Authors: Monchusi, Bernice, Ntwasa, Monde
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 10.08.2017; Public Library of Science (PLoS)
• Subjects: A549 Cells; Amino acids; Antineoplastic Agents, Phytogenic - toxicity; Apoptosis; Apoptosis - drug effects; Apoptosis Regulatory Proteins - genetics; Apoptosis Regulatory Proteins - metabolism; Biology and Life Sciences; Biotechnology; Camptothecin - analogs & derivatives; Camptothecin - toxicity; Cancer; Cancer cells; Cancer therapies; Care and treatment; Cell cycle; Cell death; Cell growth; Cell Survival - drug effects; Chemotherapy; Cytochrome; Deoxyribonucleic acid; DNA; Drug Screening Assays, Antitumor; Energy requirements; Fibroblasts; Fibroblasts - drug effects; Fibroblasts - physiology; Gene expression; Gene Expression - drug effects; Glucose; Glycolysis; GTP-binding protein; Humans; Irinotecan; Kinases; Lung cancer; Lung diseases; Medicine and Health Sciences; Metabolism; Metabolites; Mortality; Oxidative phosphorylation; p53 Protein; Phosphorylation; Physical Sciences; Protective Agents - pharmacology; Proteins; Pyruvates - pharmacology; Pyruvic acid; Research and Analysis Methods; Respiration; Senescence; Tumor cell lines; Warburg, Otto
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0182789

The 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.