Curcumin Suppresses Epithelial–Mesenchymal Transition of Renal Tubular Epithelial Cells through the Inhibition of Akt/mTOR Pathway

Zhu, Fangqiang; Chen, Minjia; Zhu, Ming; Zhao, Rongrong; Qiu, Wei; Xu, Xiang; Hong, Liu; Zhao, Hongwen; Ren, Yu; Wu, Xiongfei; Zhang, Ke‐Qin; Huang, Hong

doi:10.1248/bpb.b16-00364

Cited by 38 publications

(30 citation statements)

References 40 publications

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“…Considering curcumin as a potential anti-ageing factor it is important to mention that it could act not only by mimicking of DR and exercise but is also able to inhibit the Akt/mTOR signaling pathway (Zhu et al 2016; Guo et al 2016; Jiao et al 2016; Sikora et al 2010a). …”

Section: Introductionmentioning

confidence: 99%

Sirtuins, a promising target in slowing down the ageing process

2017

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Ageing is a plastic process and can be successfully modulated by some biomedical approaches or pharmaceutics. In this manner it is possible to delay or even prevent some age-related pathologies. There are some defined interventions, which give promising results in animal models or even in human studies, resulting in lifespan elongation or healthspan improvement. One of the most promising targets for anti-ageing approaches are proteins belonging to the sirtuin family. Sirtuins were originally discovered as transcription repressors in yeast, however, nowadays they are known to occur in bacteria and eukaryotes (including mammals). In humans the family consists of seven members (SIRT1-7) that possess either mono-ADP ribosyltransferase or deacetylase activity. It is believed that sirtuins play key role during cell response to a variety of stresses, such as oxidative or genotoxic stress and are crucial for cell metabolism. Although some data put in question direct involvement of sirtuins in extending human lifespan, it was documented that proper lifestyle including physical activity and diet can influence healthspan via increasing the level of sirtuins. The search for an activator of sirtuins is one of the most extensive and robust topic of research. Some hopes are put on natural compounds, including curcumin. In this review we summarize the involvement and usefulness of sirtuins in anti-ageing interventions and discuss the potential role of curcumin in sirtuins regulation.

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Section: Introductionmentioning

confidence: 99%

Sirtuins, a promising target in slowing down the ageing process

2017

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“…Wnt/β‐catenin and PI3K/AKT signaling pathways play important roles in the regulation of EMT, and we predicted that Mn12Ac might inhibit the EMT of breast cancer cells through regulating these two pathways. Using western blotting assay, we found that Mn12Ac significantly reduced the expressions of Wnt1 and β‐catenin (Fig a).…”

Section: Resultsmentioning

confidence: 99%

Manganese‐12 acetate suppresses the migration, invasion, and epithelial–mesenchymal transition by inhibiting Wnt/β‐catenin and PI3K/AKT signaling pathways in breast cancer cells

Xing

et al. 2018

Thoracic Cancer

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BackgroundBreast cancer is the leading cause of cancer‐related death in the world, and it is of great value to reveal the molecular mechanisms of breast cancer progression and develop new therapeutic targets.MethodsTranswell assay is used to analyze the migration and invasion of breast cancer cells. Real‐time PCR and western blotting assay are applied to detect the expression levels of epithelial–mesenchymal transition markers and the key members of Wnt/β‐catenin and PI3K/AKT signaling pathways.ResultsManganese‐12 acetate (Mn12Ac) significantly inhibited the migration and invasion of MCF7 and MDA‐MB‐231 breast cancer cells. Western blotting assay further showed that Mn12Ac significantly upregulated E‐cadherin, and downregulated N‐cadherin and vimentin. We further found that Mn12Ac reduced the mRNA expressions of epithelial–mesenchymal transition‐associated transcription factors snail, slug, twist1, and ZEB1 using real‐time PCR assay. Importantly, we further found that Mn12Ac significantly reduced the Wnt1 and β‐catenin protein expressions, and suppressed the phosphorylation of PI3K and AKT in MCF7 and MDA‐MB‐231 breast cancer cells. Very interestingly, we also showed that Mn12Ac decreased the mRNA and protein expressions of programmed cell death ligand 1.ConclusionTaken together, our results suggested that Mn12Ac inhibited the migration, invasion, and epithelial–mesenchymal transition by regulating Wnt/β‐catenin and PI3K/AKT signaling pathways in breast cancer.

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“…Curcumin's mediation of the AKT signaling pathways plays protective roles in multiple organs and with ischemia‐reperfusion injury. Zhu et al () study demonstrated that curcumin suppresses the epithelial‐mesenchymal transition of renal tubular epithelial cells through inhibition of the Akt/mTOR pathway. Thus, we asked whether the APPL1/Akt signaling pathway mediated the pathogenesis of IR‐induced latefibrosis in vitro.…”

Section: Discussionmentioning

confidence: 99%

Curcumin alleviates ischemia reperfusion‐induced late kidney fibrosis through the APPL1/Akt signaling pathway

Chen

Fan

Huang

et al. 2018

Journal Cellular Physiology

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As a major cause of renal failure, transient renal ischemia and reperfusion induce both acute kidney injury and late fibrosis, which are the common pathological manifestations of end-stage renal disease. Curcumin is a biologically active polyphenolic compound found in turmeric. Increasing evidence has demonstrated that curcumin has a protective action against renal fibrosis, whereas mechanisms underlying the anti-fibrosis role of curcumin remain poorly defined. Here, we found that APPL1, an important intracellular binding partner for AdipoR, was involved in the pathogenesis of acute injury or fibrosis and was significantly upregulated by curcumin in a mouse model of ischemia reperfusion-induced late kidney fibrosis. Moreover, Akt signaling was the specific signaling pathway identified downstream of APPL1 in the pathogenesis of fibrosis. Our in vitro experiment demonstrated that curcumin alleviates ischemia reperfusion-induced late kidney fibrosis via the APPL1/Akt pathway. These data are helpful for understanding the anti-fibrosis mechanism of curcumin in the pathogenesis of AKI-induced late fibrosis.

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Curcumin Suppresses Epithelial–Mesenchymal Transition of Renal Tubular Epithelial Cells through the Inhibition of Akt/mTOR Pathway

Cited by 38 publications

References 40 publications

Sirtuins, a promising target in slowing down the ageing process

Sirtuins, a promising target in slowing down the ageing process

Manganese‐12 acetate suppresses the migration, invasion, and epithelial–mesenchymal transition by inhibiting Wnt/β‐catenin and PI3K/AKT signaling pathways in breast cancer cells

Curcumin alleviates ischemia reperfusion‐induced late kidney fibrosis through the APPL1/Akt signaling pathway

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