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

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dc.citation.doi10.1371/journal.pone.0182789en_ZA
dc.citation.issue8en_ZA
dc.contributor.authorMonchusi, B.
dc.contributor.authorNtwasa, M.
dc.date.accessioned2017-10-18T12:43:31Z
dc.date.available2017-10-18T12:43:31Z
dc.date.issued2017-08
dc.description.abstractThe 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_ZA
dc.description.librarianEM2017en_ZA
dc.funderThis study is funded by the National Research Foundationen_ZA
dc.identifier.citationMonchusi, 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 e0182789en_ZA
dc.identifier.issn1932-6203 (Online)
dc.identifier.urihttp://hdl.handle.net/10539/23271
dc.journal.titlePLOS ONEen_ZA
dc.journal.volume12en_ZA
dc.language.isoenen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.rights© 2017 Monchusi, Ntwasa. This is an open access article distributed under the terms of the Creative Commons Attribution License.en_ZA
dc.subjectGlycolysisen_ZA
dc.subjectOxidative phosphorylationen_ZA
dc.subjectCanceren_ZA
dc.subjectExogenous pyruvateen_ZA
dc.subjectMethyl pyruvateen_ZA
dc.subjectExogenous pyruvateen_ZA
dc.subjectFibroblast cellen_ZA
dc.subjectChemotherapyen_ZA
dc.subjectMODULATE EXPRESSIONen_ZA
dc.subjectAEROBIC GLYCOLYSISen_ZA
dc.subjectBINDING-PROTEINen_ZA
dc.subjectETHYL PYRUVATEen_ZA
dc.subjectP53en_ZA
dc.subjectCYCLEen_ZA
dc.subjectRESPIRATIONen_ZA
dc.subjectMETABOLISMen_ZA
dc.subjectSENESCENCEen_ZA
dc.titleMethyl pyruvate protects a normal lung fibroblast cell line from irinotecan-induced cell death: Potential use as adjunctive to chemotherapyen_ZA
dc.typeArticleen_ZA
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