Aspirin impairs acetyl-coenzyme A metabolism in redox-compromised yeast cells

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.

Arachidonic acid alleviates the detrimental effects of acetylsalicylic acid on human granulosa cells performance in vitro

“…In agreement with previous experiments, it has been shown that ASA could increase the synthesis of different PGs, such as PGE 2 and PGI (Du, Pan, Duan, Yang, & Ge, 2016). In contrast, Farrugia et al showed that the suppression of acetyl‐CoA metabolic pathways after treatment with ASA could abort the normal synthesis of FF (Farrugia et al, 2019). Although 0.5 mM ASA was not able to make any significant reduction on PGE 2 levels while dramatically decreased (1,000‐fold) E 2 levels and ER protein, which showed a great significant role in early antral to large antral progression, estradiol production and ovulation (Emmen et al, 2005).…”

In S. cerevisiae hydroxycitric acid antagonizes chronological aging and apoptosis regardless of citrate lyase

“…They inhibits EP300 and protein acetylations and can activate autophagy [5][6][7]. In MnSOD-deficient yeast cells aspirin/salicylate starve the mitochondria of acetyl-CoA, inducing cell death [8]. In WT yeast cells salicylate can alter the balance between cell quiescence, death and proliferation as a function of metabolic signals [9].…”

Aspirin damages the cell wall of Saccharomyces cerevisiae by inhibiting the expression and activity of dolichol‐phosphate mannose synthase 1

“…aspirin impairs acetyl-coenzyme A metabolism and causes mitochondrial damage, resulting in yeast cell death [5]. However, the molecular mechanism underlying the antifungal effect of aspirin is still unclear.…”