Naringenin inhibits autophagy and epithelial‐mesenchymal transition of human lens epithelial cells by regulating the Smad2/3 pathway

Li, Qingnan; Liu, Shuang; Yang, Guang; Li, Mingming; Qiao, Peng; Xue, Qiang

doi:10.1002/ddr.21868

Cited by 7 publications

(6 citation statements)

References 29 publications

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“…All the compounds that might participate in the regulatory processes of JPYSF in EMT were considered as potential active ingredients. In support of this, several previous studies have shown that quercetin ( Elumalai et al, 2021 ), kaempferol ( Ji et al, 2020 ), luteolin ( Cao et al, 2020 ), naringenin ( Li et al, 2021 ), isorhamnetin, Tanshinone IIA ( Fu et al, 2021 ), cryptotanshinone ( Zhang Z et al, 2020 ), and aloe-emodin ( Liu et al, 2021 ) had well-established roles in EMT . Taken together, our results demonstrate that the core components may be the effective ingredients of JPYSF for the EMT treatment.…”

Section: Discussionmentioning

confidence: 59%

Network Pharmacology and Experimental Verification Strategies to Illustrate the Mechanism of Jian-Pi-Yi-Shen Formula in Suppressing Epithelial–Mesenchymal Transition

Zhao

Wang

et al. 2022

Front. Pharmacol.

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Jian-Pi-Yi-Shen formula (JPYSF), a traditional Chinese medicine, has been recommended to treat renal fibrosis for decades. Previous studies had shown that JPYSF could inhibit epithelial–mesenchymal transition (EMT), an important regulatory role in renal fibrosis. However, the mechanism of JPYSF action is largely unknown. In this study, network pharmacology and experimental verification were combined to elucidate and identify the potential mechanism of JPYSF against renal fibrosis by suppressing EMT at molecular and pathway levels. Network pharmacology was first performed to explore the mechanism of JPYSF against renal fibrosis targeting EMT, and then a 5/6 nephrectomy (5/6 Nx)-induced rat model of renal fibrosis was selected to verify the predictive results by Masson’s trichrome stains and western blot analysis. Two hundred and thirty-two compounds in JPYSF were selected for the network approach analysis, which identified 137 candidate targets of JPYSF and 4,796 known therapeutic targets of EMT. The results of the Gene Ontology (GO) function enrichment analysis included 2098, 88, and 133 GO terms for biological processes (BPs), molecular functions (MFs), and cell component entries, respectively. The top 10 enrichment items of BP annotations included a response to a steroid hormone, a metal ion, oxygen levels, and so on. Cellular composition (CC) is mainly enriched in membrane raft, membrane microdomain, membrane region, etc. The MF of JPYSF analysis on EMT was predominately involved in proximal promoter sequence-specific DNA binding, protein heterodimerization activity, RNA polymerase II proximal promoter sequence-specific DNA binding, and so on. The involvement signaling pathway of JPYSF in the treatment of renal fibrosis targeting EMT was associated with anti-fibrosis, anti-inflammation, podocyte protection, and metabolism regulation. Furthermore, the in vivo experiments confirmed that JPYSF effectively ameliorated interstitial fibrosis and inhibited the overexpression of α-SMA, Wnt3a, and β-catenin, and increased the expression of E-cadherin by wnt3a/β-catenin signaling pathway in 5/6 Nx-induced renal fibrosis rats. Using an integrative network pharmacology-based approach and experimental verification, the study showed that JPYSF had therapeutic effects on EMT by regulating multi-pathway, among which one proven pathway was the Wnt3a/β-catenin signaling pathway. These findings provide insights into the renoprotective effects of JPYSF against EMT, which could suggest directions for further research of JPYSF in attenuating renal fibrosis by suppressing EMT.

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Section: Discussionmentioning

confidence: 59%

Network Pharmacology and Experimental Verification Strategies to Illustrate the Mechanism of Jian-Pi-Yi-Shen Formula in Suppressing Epithelial–Mesenchymal Transition

Zhao

Wang

et al. 2022

Front. Pharmacol.

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“…Increased E-cadherin and decreased MMP-9 expression were observed in the present study following MSpf treatment. In addition, recent studies have suggested that autophagy and EMT are associated with regulation of tumorigenesis and tumor progression ( 46 , 47 ). Taken together, these results suggested that MSpf treatment regulated induction of autophagy and suppression of EMT in DLD-1 cells and that MSpf treatment may be a valuable therapeutic strategy for CRC.…”

Section: Discussionmentioning

confidence: 99%

Protein components of maple syrup as a potential resource for the development of novel anti‑colorectal cancer drugs

Yamamoto,

Shiburo,

Moriyama

et al. 2023

Oncol Rep

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Maple syrup is a natural sweetener consumed worldwide. Active ingredients of maple syrup possess antitumor effects; however, these ingredients are phenolic compounds. The present study aimed to investigate components other than phenolic compounds that may have antitumor effects against colorectal cancer (CRC). Cell proliferation assays demonstrated that treatment with the more than 10,000 molecular weight fraction significantly inhibited viability in DLD-1 cells. Therefore, we hypothesized that the protein components of maple syrup may be the active ingredients in maple syrup. We obtained protein components from maple syrup by ammonium sulfate precipitation, and treatment with the protein fraction of maple syrup (MSpf) was found to exhibit a potential antitumor effect. MSpf-treated DLD-1 colon adenocarcinoma cells exhibited significantly decreased proliferation, migration and invasion. In addition, upregulation of LC3A and E-cadherin and downregulation of MMP-9 expression levels were observed following MSpf treatment. Investigation of the components of MSpf suggested that it was primarily formed of advanced glycation end products (AGEs). Therefore, whether AGEs in MSpf affected the STAT3 pathway through the binding to its receptor, receptor of AGE (RAGE), was assessed. MSpf treatment was associated with decreased RAGE expression and STAT3 phosphorylation. Finally, to determine whether autophagy contributed to the inhibitory effect of cell proliferation following MSpf treatment, the effect of MSpf treatment on autophagy induction following bafilomycin A1 treatment, a specific autophagy inhibitor, was assessed. The inhibitory effect of MSpf treatment on cell proliferation was enhanced through the inhibition of autophagy by bafilomycin A1 treatment. These results suggested that AGEs in MSpf suppressed cell proliferation and epithelial-mesenchymal transition through inhibition of the STAT3 signaling pathway through decreased RAGE expression. Therefore, AGEs in MSpf may be potential compounds for the development of antitumor drugs for the treatment of CRC with fewer adverse effects compared with existing antitumor drugs.

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“…Autophagy is a major process that contributes to the maintenance of intracellular energy metabolism and self‐survival 18 . Recently, it has been demonstrated that autophagy and EMT are tightly correlated in regulating tumorigenesis and tumour progression 19,20 . During the initial stage of tumour, autophagy suppresses cancer invasion and metastasis by selectively degrading important signalling molecules in the EMT process 19 .…”

Section: Discussionmentioning

confidence: 99%

“…18 Recently, it has been demonstrated that autophagy and EMT are tightly correlated in regulating tumorigenesis and tumour progression. 19,20 During the initial stage of tumour, autophagy suppresses cancer invasion and metastasis by selectively degrading important signalling molecules in the EMT process. 19 In contrast, during the process of tumour metastasis and diffusion, cancer cells need to activate autophagy to obtain sufficient energy and promote EMT.…”

Section: Discussionmentioning

confidence: 99%

Larotrectinib induces autophagic cell death through AMPK/mTOR signalling in colon cancer

Kong

Zhu

Zheng

et al. 2022

J Cellular Molecular Medi

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Larotrectinib (Lar) is a highly selective and potent small-molecule inhibitor used in patients with tropomyosin receptor kinase (TRK) fusion-positive cancers, including colon cancer. However, the underlying molecular mechanisms specifically in patients with colon cancer have not yet been explored. Our data showed that Lar significantly suppressed proliferation and migration of colon cancer cells. In addition, Lar suppressed the epithelial-mesenchymal transition (EMT) process, as evidenced by elevation in E-cadherin (E-cad), and downregulation of vimentin and matrix metalloproteinase (MMP) 2/9 expression. Furthermore, Lar was found to activate autophagic flux, in which Lar increased the ratio between LC3II/LC3I and decreased the expression of p62 in colon cancer cells. More importantly, Lar also increased AMPK phosphorylation and suppressed mTOR phosphorylation in colon cancer cells. However, when we silenced AMPK in colon cancer cells, Lar-induced accumulation of autolysomes as well as Lar-induced suppression of the EMT process were significantly diminished. An in vivo assay also confirmed that tumour volume and weight decreased in Lar-treated mice than in control mice. Taken together, this study suggests that Lar significantly suppresses colon cancer proliferation and migration by activating AMPK/mTORmediated autophagic cell death.

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Naringenin inhibits autophagy and epithelial‐mesenchymal transition of human lens epithelial cells by regulating the Smad2/3 pathway

Cited by 7 publications

References 29 publications

Network Pharmacology and Experimental Verification Strategies to Illustrate the Mechanism of Jian-Pi-Yi-Shen Formula in Suppressing Epithelial–Mesenchymal Transition

Network Pharmacology and Experimental Verification Strategies to Illustrate the Mechanism of Jian-Pi-Yi-Shen Formula in Suppressing Epithelial–Mesenchymal Transition

Protein components of maple syrup as a potential resource for the development of novel anti‑colorectal cancer drugs

Larotrectinib induces autophagic cell death through AMPK/mTOR signalling in colon cancer

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