Suppressing Cyclooxygenase-2 Prevents nonalcoholic and inhibits apoptosis of hepatocytes that are involved in the Akt/p53 signal pathway

Wu, Jialing; Chen, Chong; Hu, Xi; Cai, Xianbin; Guan, Yinghong; Hu, Hui; Wang, Qinjia; Chen, Xiaofeng; Cai, Bin; Jing, Xubin

doi:10.1016/j.bbrc.2015.12.096

Cited by 17 publications

(14 citation statements)

References 25 publications

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“…In the present study, we have demonstrated that upregulation of FOXA1 blocks AKT pathway activation and is accompanied by changes in the expression of several key senescence-associated genes (p16, p27 and PTEN) in EC cells. Although our knowledge of specific mechanism of cell senescence in EC reported is limited, AKT has been shown to protect against RAS-induced senescence in other cell types (24), and several classical transcription factors related to senescence have been identified, including p16, p21 and p53 (25)(26)(27). Based on our findings, we suggest that FOXA1 promotes cell senescence in EC by interaction with p16…”

Section: Discussionmentioning

confidence: 52%

Forkhead-box A1 induces cell senescence in endometrial cancer by regulating p16INK4a

et al. 2016

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Abstract. We previously identified FOXA1 as a tumorsuppressor in EC cells. In the present study, we sought to delineate the different roles of FOXA1 associated with cell senescence and further investigated the correlation between FOXA1 and p16INK4a in the progression of EC. Using reverse transcription-quantitative PCR (RT-qPCR), we found that FOXA1 expression was significantly downregulated in EC cells compared to that in normal endometrial cells. Functionally, senescence-associated β-galactosidase staining, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), clonogenic and Transwell assays showed that in addition to acting as a pioneer factor, FOXA1 was significantly upregulated in senescent EC cells. Furthermore, restoration of FOXA1 expression triggered multiple steps of cellular senescence in EC cells and activated p16INK4a expression. All of these findings indicate that FOXA1 promotes cell senescence in EC by interaction with p16INK4a , possibly via the AKT pathway. Notably, a selective PI3K inhibitor raised the possibility that FOXA1-induced senescence is associated with the AKT pathway in EC cells. Collectively, the present study provides a conceivable molecular mechanism by which cell senescence acts as the barrier to EC, and is regulated by FOXA1-induced p16INK4a expression. This may be a newly identified regulatory mechanism of cell senescence in EC.

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Section: Discussionmentioning

confidence: 52%

Forkhead-box A1 induces cell senescence in endometrial cancer by regulating p16INK4a

et al. 2016

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“…Subbaramaiah et al reported that P53 inhibited the expression of COX-2, while a mutation in TP53 resulted in an increase in COX-2 activity ( Subbaramaiah et al, 1999 ). Wu et al found that COX-2 inhibits apoptosis via P53 signaling ( Wu et al, 2016 ). In this study, we found that MIF was associated with P53 in clinical samples.…”

Section: Discussionmentioning

confidence: 99%

The role of macrophage migration inhibitory factor in promoting benign prostatic hyperplasia epithelial cell growth by modulating COX-2 and P53 signaling

et al. 2020

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Inflammation and proinflammatory cytokines have been implicated in the progression of benign prostatic hyperplasia (BPH). Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine. Our previous study found that MIF is highly expressed in BPH epithelium. It has been reported that there is a correlation between MIF and clinical BPH progression. However, whether MIF has an effect on BPH epithelial cells is not clear. The aim of this study was to explore whether MIF has a role in BPH. Our results showed that IHC showed that MIF is highly expressed in the epithelium and that MIF and PCNA expression levels are higher in BPH samples than in control. CCK8 and flow cytometry assays showed that rMIF promoted the proliferation of BPH-1 and PWR-1E cells, while ISO-1 partially reversed this effect on proliferation. JC-1 assays showed that rMIF inhibited the apoptosis of BPH-1 and PWR-1E cells, and ISO-1 could partially reverse this inhibition. Moreover, western blotting indicated that rMIF downregulated P53 and upregulated COX-2. Furthermore, MIF-induced proliferation could be inhibited by celecoxib in the CCK8 and flow cytometry assay. MIF-inhibited apoptosis could be partially reversed by celecoxib in the JC-1 assay. Western blotting showed that celecoxib could partially reverse MIF-induced COX-2 upregulation and P53 downregulation. Together, MIF is highly expressed in BPH epithelium. In vitro, MIF promoted BPH epithelial cell growth by regulating COX-2 and P53 signaling. Targeting MIF may provide a new option for the improved treatment of BPH in the future.

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“…It was suggested that celecoxib could attenuate liver steatosis and inflammation in NAFLD (Chen et al, ) by suppression of non‐canonical Wnt signaling pathway and regulation of NF‐kB pathway (Tian, Zhang, Li, & Xie, ). Celecoxib may also inhibit hepatocytes apoptosis and protect hepatocytes from palmitate‐induced insulin resistance through the Akt/p53 signal pathway (Chen et al, ; Wu et al, ).…”

Section: Discussionmentioning

confidence: 99%

Role of anti‐inflammatory interventions in high‐fat‐diet‐induced obesity

Ghazala

Medney

Meleis

et al. 2020

Biomedical Chromatography

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Lipotoxicity is defined as deposition of excess fat associated with an inflammatory response. Metabolomic analysis of fatty acids (FAs) can be a marker of silent inflammation. ω3‐Enriched diet, celecoxib, and safranal may have a protective anti‐inflammatory role. In this work, total FAs extracted from red blood cells and arachidonic acid‐to‐eicosapentaenoic acid (AA‐to‐EPA) ratios were assessed using GC–MS assay in single‐ion monitoring mode. The study was conducted on 64 male rats divided into eight groups: I, controls; II, rats received high‐fat diet (HFD), III, rats received ω‐6‐enriched HFD; IV, rats received ω‐3‐enriched HFD; V, rats received celecoxib with HFD; VI, rats received safranal with HFD; VII and VIII, rats received celecoxib and safranal with ω‐3 HFD, respectively. GC–MS Gas chromatography Mass spectrometry was performed for analysis of fatty acid methyl ester. Enzyme‐linked immunosorbent assay was used to analyze serum interleukin‐6 (IL‐6) and transforming growth factor‐beta 1 (TGF‐β1) concentrations. A statistically significant decrease of AA‐to‐EPA ratio was observed in group VII when compared with the groups receiving HFDs. This group also showed the lowest serum IL‐6 level and highest TGF‐β1 level. In conclusion, ω3‐enriched diet along with drugs (e.g. celecoxib) and herbal medications (e.g. safranal) may have an anti‐inflammatory effect in lipotoxicity. GC–MS with single‐ion monitoring is valid for the analysis of FAs.

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Suppressing Cyclooxygenase-2 Prevents nonalcoholic and inhibits apoptosis of hepatocytes that are involved in the Akt/p53 signal pathway

Cited by 17 publications

References 25 publications

Forkhead-box A1 induces cell senescence in endometrial cancer by regulating p16INK4a

Forkhead-box A1 induces cell senescence in endometrial cancer by regulating p16INK4a

The role of macrophage migration inhibitory factor in promoting benign prostatic hyperplasia epithelial cell growth by modulating COX-2 and P53 signaling

Role of anti‐inflammatory interventions in high‐fat‐diet‐induced obesity

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