Aspirin Promotes Oligodendroglial Differentiation Through Inhibition of Wnt Signaling Pathway

Huang, Nanxin; Dong, Chen; Wu, Xutong; Chen, Xianjun; Zhang, Xuesi; Niu, Jianqin; Shen, Hai‐Ying; Xiao, Lan

doi:10.1007/s12035-015-9241-z

Cited by 16 publications

(18 citation statements)

References 38 publications

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“…Previous studies have reported that aspirin affects cells through the JAK1/STAT1 pathway, ERK1/2 activation, and the canonical Wnt/β-catenin pathway [36][37][38][39]. Among these pathways, the canonical Wnt/β-catenin signaling pathway is a highly conserved pathway related to cell growth, development, metabolism, and stem cell maintenance.…”

Section: Discussionmentioning

confidence: 99%

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

Wang

Tang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used in clinical practice to relieve fever and pain. Aspirin, as a representative NSAID, has been widely used in the treatment of tendinopathy. Some reports have demonstrated that aspirin can induce apoptosis in cancer cells. However, evidence regarding aspirin treatment for tendinopathy, especially the effect of this treatment on tendon stem cells (TSCs), is lacking. Understanding the effect of aspirin on tendinopathy may provide a basis for the rational use of NSAIDs in clinical practice. The aim of our study was to determine whether aspirin induces apoptosis in rat TSCs via the Wnt/β-catenin pathway. Methods: First, we used flow cytometry and fluorescence to detect TSC apoptosis. Protein expression of the apoptosis-related caspase-3 pathway was investigated via western blot analysis. Next, we used western blotting to determine the effect of aspirin on the Wnt/β-catenin pathway. We used immunostaining to detect the levels of Bcl2, cleaved caspase-3, and P-β-catenin in the Achilles tendon. Finally, we used flow cytometry, fluorescence, and western blotting to investigate the aspirin-induced apoptosis of TSCs via the Wnt/β-catenin pathway. Results: Aspirin induced morphological apoptosis in rat TSCs via the mitochondrial/caspase-3 pathway and induced cellular apoptosis in the Achilles tendon. Apoptosis was partly reversed after adding the Wnt signaling activator Wnt3a and lithium chloride (LiCl, a GSK-3β inhibitor). Aspirin administration led to a dose-dependent increase in COX-2 expression. Apoptosis was promoted after adding the COX-2 inhibitor NS398. Conclusion: The Wnt/β-catenin pathway plays a vital role in aspirin-induced apoptosis by regulating mitochondrial/caspase-3 function. Elevating COX-2 levels may protect cells against apoptosis. More importantly, the results remind us to consider the apoptotic effect of aspirin on TSCs and tendon cells when aspirin is administered to treat tendinopathy. The relationship between the positive and negative effects of aspirin remains a subject for future study.

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Section: Discussionmentioning

confidence: 99%

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

Wang

Tang

et al. 2018

Cell Physiol Biochem

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“…Co‐treatment with Aspirin and DHA suppressed activation of microglia in vitro and increased the microglial concentration of glutathione; therefore, increasing the antioxidant capacity of microglia cells (Pettit, Varsanyi, Tadros, & Vassiliou, ). Two studies using a combination of an in vivo model of white matter lesions and in vitro oligodendrocyte precursor cells demonstrated aspirin can protect white matter from insult (Chen et al, ; Huang et al, ). Aspirin appears to promote oligodendrocyte differentiation to repair white matter lesions possibly via inhibition of Wnt/β‐Catenin signalling, a regulator of cell fate.…”

Section: Resultsmentioning

confidence: 99%

Putative neuroprotective pharmacotherapies to target the staged progression of mental illness

Robertson

Coronado

Sethi

et al. 2019

Early Intervention Psych

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Aim: Neuropsychiatric disorders including depression, bipolar and schizophrenia frequently exhibit a neuroprogressive course from prodrome to chronicity. There are a range of agents exhibiting capacity to attenuate biological mechanisms associated with neuroprogression. This review will update the evidence for putative neuroprotective agents including clinical efficacy, mechanisms of action and limitations in current assessment tools, and identify novel agents with neuroprotective potential.Method: Data for this review were sourced from online databases PUBMED, Embase and Web of Science. Only data published since 2012 were included in this review, no data were excluded based on language or publication origin.Results: Each of the agents reviewed inhibit one or multiple pathways of neuroprogression including: inflammatory gene expression and cytokine release, oxidative and nitrosative stress, mitochondrial dysfunction, neurotrophin dysregulation and apoptotic signalling. Some demonstrate clinical efficacy in preventing neural damage or loss, relapse or cognitive/functional decline. Agents include: the psychotropic medications lithium, second generation antipsychotics and antidepressants; other pharmacological agents such as minocycline, aspirin, cyclooxygenase-2 inhibitors, statins, ketamine and alpha-2-delta ligands; and others such as erythropoietin, oestrogen, leptin, N-acetylcysteine, curcumin, melatonin and ebselen.Conclusions: Signals of evidence of clinical neuroprotection are evident for a number of candidate agents. Adjunctive use of multiple agents may present a viable avenue to clinical realization of neuroprotection. Definitive prospective studies of neuroprotection with multimodal assessment tools are required.

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“…Activation of Wnt signaling also negatively regulates OL lineage development, including specification of OPCs from NSCs and terminal differentiation of OLs [42]. In addition, our previous work showed that selective activation of the Wnt/β-catenin signaling pathway by QS11 can suppress OL differentiation [43]. In line with the aforementioned findings, we showed here that QUE's effect on GSCs can also be attenuated by QS11, a selective agonist of the Wnt/β-catenin signaling pathway; this indicates that QUE-induced bioprocesses in GSCs are likely mediated via the Wnt signaling pathway and suggests a potential application of QUE to induce OL-oriented differentiation for enhanced effectiveness in chemotherapy of glioma.…”

Section: Discussionmentioning

confidence: 99%

“…Cells grown on coverslips were fixed with 4% paraformaldehyde for immunocytochemistry evaluation according to our previous study [43]. After being incubated with 1% bovine serum albumin (BSA)/0.3% Triton X-100 for 10 min to block non-specific reactions, cells were incubated with primary antibodies (see Table 1) overnight at 4°C followed by an incubation of secondary antibodies (see Table 2) for 2-3 h at room temperature (RT).…”

Section: Methodsmentioning

confidence: 99%

Promoting oligodendroglial-oriented differentiation of glioma stem cell: a repurposing of quetiapine for the treatment of malignant glioma

et al. 2017

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As a major contributor of chemotherapy resistance and malignant recurrence, glioma stem cells (GSCs) have been proposed as a target for the treatment of gliomas. To evaluate the therapeutic potential of quetiapine (QUE), an atypical antipsychotic, for the treatment of malignant glioma, we established mouse models with GSCs-initiated orthotopic xenograft gliomas and subcutaneous xenograft tumors, using GSCs purified from glioblastoma cell line GL261. We investigated antitumor effects of QUE on xenograft gliomas and its underlying mechanisms on GSCs. Our data demonstrated that (i) QUE monotherapy can effectively suppress GSCs-initiated tumor growth; (ii) QUE has synergistic effects with temozolomide (TMZ) on glioma suppression, and importantly, QUE can effectively suppress TMZ-resistant (or -escaped) tumors generated from GSCs; (iii) mechanistically, the anti-glioma effect of QUE was due to its actions of promoting the differentiation of GSCs into oligodendrocyte (OL)-like cells and its inhibitory effect on the Wnt/β-catenin signaling pathway. Together, our findings suggest an effective approach for anti-gliomagenic treatment via targeting OL-oriented differentiation of GSCs. This also opens a door for repurposing QUE, an FDA approved drug, for the treatment of malignant glioma.

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Aspirin Promotes Oligodendroglial Differentiation Through Inhibition of Wnt Signaling Pathway

Cited by 16 publications

References 38 publications

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

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

Putative neuroprotective pharmacotherapies to target the staged progression of mental illness

Promoting oligodendroglial-oriented differentiation of glioma stem cell: a repurposing of quetiapine for the treatment of malignant glioma

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