Dataset Information

20(S)-Protopanaxadiol Inhibits Angiotensin II-Induced Epithelial- Mesenchymal Transition by Downregulating SIRT1.

ABSTRACT: 20(S)-Protopanaxadiol (PPD) is one of the major active metabolites in ginseng saponin. Our previous studies revealed a broad spectrum of antitumor effects of PPD. Angiotensin II (Ang II), the biologically active peptide of the renin-angiotensin system (RAS), plays a critical role in the metastasis of various cancers. However, its role in the anti-metastatic effects of PPD is not clearly understood. In this study, we investigated the inhibitory effect of PPD on Ang II-induced epithelial-mesenchymal transition (EMT) in non-small cell lung cancer (NSCLC) cells, and the potential molecular mechanisms of suppression of NSCLC migration and metastasis by PPD. Treatment of A549 cells with Ang II increased metastases in an experimental model of cancer metastasis in vivo. PPD effectively prevented Ang II-induced EMT, as indicated by upregulation of E-cadherin and downregulation of vimentin. Additionally, Ang II upregulated the class III deacetylase sirtuin 1 (SIRT1) expression in EMT progression, while downregulation of SIRT1 was involved in suppression of Ang II-induced EMT by PPD. Moreover, the inhibitory effect of PPD was reversed by SIRT1 upregulation, and PPD demonstrated synergy with an SIRT1 inhibitor on Ang II-induced EMT. Taken together, our data reveal the mechanism of the anti-metastatic effects of PPD on Ang II-induced EMT and indicate that PPD can be used as an effective anti-tumor treatment.

SUBMITTER: Wang Y

PROVIDER: S-EPMC6514190 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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20(<i>S</i>)-Protopanaxadiol Inhibits Angiotensin II-Induced Epithelial- Mesenchymal Transition by Downregulating SIRT1.

Wang Yuchen Y Xu Huali H Fu Wenwen W Lu Zeyuan Z Guo Minyu M Wu Xueji X Sun Mingyang M Liu Yanzhe Y Yu Xiaofeng X Sui Dayun D

Frontiers in pharmacology 20190507

20(<i>S</i>)-Protopanaxadiol (PPD) is one of the major active metabolites in ginseng saponin. Our previous studies revealed a broad spectrum of antitumor effects of PPD. Angiotensin II (Ang II), the biologically active peptide of the renin-angiotensin system (RAS), plays a critical role in the metastasis of various cancers. However, its role in the anti-metastatic effects of PPD is not clearly understood. In this study, we investigated the inhibitory effect of PPD on Ang II-induced epithelial-me ...[more]

PMID: 31133857

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Project description:The limb-bud and heart (LBH) gene was reported to suppress nasopharyngeal carcinoma (NPC) progression in our previous study. Distant metastasis predominantly accounts for the unsatisfactory prognosis of NPC treatment, in which epithelial-mesenchymal transition (EMT) and tumor angiogenesis are of great significance. The roles of exosomes in mediating NPC progression have been highlighted in recent researches, and attempts have been made to explore the clinical application of NPC exosomes. Here we investigated the function of the LBH gene in NPC exosomes, and its potential mechanism. NPC xenografts were constructed, showing that vascular endothelial growth factor A (VEGFA) expression and neovascularity were attenuated by LBH overexpression, together with diminished EMT progression. NPC-derived exosomes were isolated, identified and applied for in vitro/in vivo experiments, and the exosomal distribution of LBH was elevated in exosomes derived from LBH-upregulated cells. Ectopic LBH, αB-crystallin (CRYAB) and VEGFA expression was induced by lentiviral infection or plasmid transfection to explore their functions in modulating EMT and angiogenesis in NPC. The addition of LBH+ NPC exosomes during a Matrigel plug assay in mice suppressed in vivo angiogenesis, and the treatment of human umbilical vein endothelial cells (HUVECs) with LBH+ NPC exosomes inhibited cellular proliferation, migration and tube formation. The interactions among LBH, CRYAB and VEGFA were confirmed by colocalization and fluorescence resonance energy transfer (FRET) assays, and extracellular VEGFA secretion from both HUVECs and NPC cells under the treatment with LBH+ NPC exosomes was diminished according to ELISA results. We concluded that exosomal LBH inhibits EMT progression and angiogenesis in the NPC microenvironment, and that its effects are partially implemented by modulation of VEGFA expression, secretion and related signaling. Thus, LBH could serve as a promising therapeutic target in VEGFA-focused NPC treatment.

Dataset Information

20(S)-Protopanaxadiol Inhibits Angiotensin II-Induced Epithelial- Mesenchymal Transition by Downregulating SIRT1.

Publications

20(<i>S</i>)-Protopanaxadiol Inhibits Angiotensin II-Induced Epithelial- Mesenchymal Transition by Downregulating SIRT1.

Similar Datasets

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