GROWTH INHIBITION OF MESENCHYMAL STEM CELLS BY ASPIRIN: INVOLVEMENT OF THE WNT/β‐CATENIN SIGNAL PATHWAY

Abstract

1. Mesenchymal stem cell (MSC) therapy is drawing increasing attention in cardiology. However, the effect of aspirin, an assistant medication used extensively in the treatment of cardiovascular diseases, on MSC is not clear. 2. In the present study, we investigated the effect of aspirin on the growth of MSC in vitro and the underlying mechanism of its action. 3. The 3-(4,5-dimethyl-2 thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay revealed that 1, 5 and 10 mmol/L aspirin inhibited the growth of MSC by 18, 37 and 62%, respectively. DNA synthesis of MSC was inhibited by 25, 57 and 90% following treatment with 1, 5 and 10 mmol/L aspirin, respectively, as determined by the tritiated thymidine incorporation assay. No cytotoxicity was observed based on Trypan blue dye exclusion and cell morphological observations. Western blot analysis demonstrated that the protein level of phosphorylated beta-catenin increased, whereas that of cyclin D1 decreased, after treatment of MSC with aspirin. Cell cycle analysis showed that aspirin failed to significantly alter the proportion of cells in different stages of the cell cycle. 4. These observations indicate that aspirin inhibits MSC proliferation and that the downregulation of the wnt/beta-catenin signal pathway may be involved in the growth inhibition of MSC by aspirin.

High Concentration of Aspirin Induces Apoptosis in Rat Tendon Stem Cells via Inhibition of the Wnt/β-Catenin Pathway

“…Therefore, we observed the changes in levels of Bcl2, BAX, and cleaved caspase-3 in rat TSCs and determined that aspirin-induced apoptosis occurs through the mitochondrial/ caspase-3 pathway. Our results from this study are similar to those found in previous research [32][33][34][35]. We confirmed our results using an immunofluorescence assay in rat Achilles tendons.…”

“…Li et al revealed that the canonical Wnt/β-catenin pathway inhibits the apoptosis of tumor cells and mesenchymal stem cells [40] and modulates the differentiation of stem cells [31][32]. Therefore, we next investigated the role of the canonical Wnt/β-catenin pathway in aspirin-induced TSC apoptosis.…”

The effect of metamizole and tolfenamic acid on canine and equine adipose-derived mesenchymal stem cells (ASCs) an in vitro research.

“…A strong cytotoxic effect of tolfenamic acid on canine and equine stem cells was recorded in the first and last day of the culture, when cell death was detected. This finding is partially consistent with the previous study performed by Wang et al (2006), where the highest concentrations of aspirin added to the medium were effective in inhibiting the growth of MSCs, without concomitant increase in cell death. It can be assumed that the different values of proliferation observed in our study in ASCs isolated from various species may be due to the different mechanisms of drug metabolism pathways in canine and equine stem cells.…”

The birth of ‘regenerative pharmacology’: a clinical perspective

“…therapy used in interventional procedures but include oral medications that are widely used in primary and secondary prevention. For example, a 1-10 mmol·L -1 dose of aspirin has been shown to inhibit proliferation of mesenchymal stem cells (MSCs) in rats through a mechanism of action thought to involve inhibition of PGE2 formation and subsequent down-regulation of the Wnt/b-catenin signalling pathway (Wang et al, 2006). Treatment of MSCs with PGE2 increases cell proliferation and enhances the activation of the Wnt/bcatenin pathway (Kleiveland et al, 2008).…”