Please use this identifier to cite or link to this item:
Title: Aspirin impairs acetyl-coenzyme A metabolism in redox-compromised yeast cells
Authors: Farrugia, Gianluca
Azzopardi, Maria
Saliba, Christian
Grech, Godfrey
Gross, Angelina S.
Pistolic, Jelena
Benes, Vladimir
Vassallo, Neville
Borg, Joseph
Madeo, Frank
Eisenberg, Tobias
Balzan, Rena
Keywords: Isopentenoids -- Synthesis
Medicine, Popular
Cancer -- Prevention
Anti-inflammatory agents
Aspirin -- Therapeutic use
Issue Date: 2019
Publisher: Nature Publishing Group
Citation: Farrugia, G., Azzopardi, M., Saliba, C., Grech, G., Gross, A. S., Pistolic, J., . . . Balzan, R. (2019). Aspirin impairs acetyl-coenzyme A metabolism in redox-compromised yeast cells. Scientific Reports, 9(1), 6152.
Abstract: Aspirin is a widely used anti-inflammatory and antithrombotic drug also known in recent years for its promising chemopreventive antineoplastic properties, thought to be mediated in part by its ability to induce apoptotic cell death. However, the full range of mechanisms underlying aspirin’s cancer-preventive properties is still elusive. In this study, we observed that aspirin impaired both the synthesis and transport of acetyl-coenzyme A (acetyl-CoA) into the mitochondria of manganese superoxide dismutase (MnSOD)-deficient Saccharomyces cerevisiae EG110 yeast cells, but not of the wild-type cells, grown aerobically in ethanol medium. This occurred at both the gene level, as indicated by microarray and qRT-PCR analyses, and at the protein level as indicated by enzyme assays. These results show that in redox-compromised MnSOD-deficient yeast cells, but not in wild-type cells, aspirin starves the mitochondria of acetyl-CoA and likely causes energy failure linked to mitochondrial damage, resulting in cell death. Since acetyl-CoA is one of the least-studied targets of aspirin in terms of the latter’s propensity to prevent cancer, this work may provide further mechanistic insight into aspirin’s chemopreventive behavior with respect to early stage cancer cells, which tend to have downregulated MnSOD and are also redox-compromised.
Appears in Collections:Scholarly Works - FacM&SPB

Files in This Item:
File Description SizeFormat 
s41598-019-39489-4.pdf2.67 MBAdobe PDFView/Open

Items in OAR@UM are protected by copyright, with all rights reserved, unless otherwise indicated.