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Rhein inhibits malignant phenotypes of human renal cell carcinoma by impacting on MAPK/NF-?B signaling pathways.

ABSTRACT: Background:Rhein, an anthraquinone derivative of rhubarb, is traditionally used in Chinese herbal medicine. Now emerging studies suggest its antitumor properties in many human cancers. The present study aims to investigate the antitumor role of Rhein and its possible mechanism in human renal cell carcinoma (RCC). Materials and methods:Three RCC cell lines (A489, 786-O and ACHN) were used as the cell models. We applied CCK-8, cell counting, colony formation, wound healing and Transwell assays to assess the antitumor roles of Rhein in RCC cells in vitro. The therapeutic efficacy of Rhein was further evaluated by intraperitoneal administrations in tumor formation of mice. Western blot was used to investigate the underlying mechanisms of action of Rhein. Results:Rhein inhibited RCC cell proliferation in a dose- and time-dependent manner. It also suppressed RCC cell migration and invasion in vitro. Moreover, Rhein was able to inhibit tumor growth in nude mice by intraperitoneal administration in vivo. Mechanistically, the protein levels of phosphorylated MAPK (mitogen-activated protein kinase, extracellular signal-regulated kinase and c-Jun N-terminal kinase), phosphorylated Akt and two targets of NF-?B (nuclear factor kappa-light-chain enhancer of activated B cells) pathway, matrix metalloproteinase 9 and CCND1 were all markedly reduced by Rhein treatment. Conclusion:Rhein processed the antitumor effects in RCC cells by inhibiting cell proliferation, migration and invasion, and these tumor-suppressing functions might be mediated by MAPK/NF-?B signaling pathways.

SUBMITTER: Ma YL

PROVIDER: S-EPMC5857153 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Rhein inhibits malignant phenotypes of human renal cell carcinoma by impacting on MAPK/NF-κB signaling pathways.

Ma Ya-Li YL Chen Fang F Shi Jun J

OncoTargets and therapy 20180314

<h4>Background</h4>Rhein, an anthraquinone derivative of rhubarb, is traditionally used in Chinese herbal medicine. Now emerging studies suggest its antitumor properties in many human cancers. The present study aims to investigate the antitumor role of Rhein and its possible mechanism in human renal cell carcinoma (RCC).<h4>Materials and methods</h4>Three RCC cell lines (A489, 786-O and ACHN) were used as the cell models. We applied CCK-8, cell counting, colony formation, wound healing and Trans ...[more]

PMID: 29559796

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Project description:Salidroside (Sal) is an active ingredient that is isolated from Rhodiola rosea, which has been reported to have anti-inflammatory activities and a renal protective effect. However, the role of Sal on renal fibrosis has not yet been elucidated. Here, the purpose of the current study is to test the protective effects of Sal against renal interstitial fibrosis (RIF), and to explore the underlying mechanisms using both in vivo and in vitro models. In this study, we establish the unilateral ureteric obstruction (UUO) or folic acid (FA)-induced mice renal interstitial fibrosis in vivo and the transforming growth factor (TGF)-β1-stimulated human proximal tubular epithelial cell (HK-2) model in vitro. The levels of kidney functional parameters and inflammatory cytokines in serum are examined. The degree of renal damage and fibrosis is determined by histological assessment. Immunohistochemistry and western blotting are used to determine the mechanisms of Sal against RIF. Our results show that treatment with Sal can ameliorate tubular injury and deposition of the extracellular matrix (ECM) components (including collagen Ш and collagen I). Furthermore, Sal administration significantly suppresses epithelial-mesenchymal transition (EMT), as evidenced by a decreased expression of α-SMA, vimentin, TGF-β1, snail, slug, and a largely restored expression of E-cadherin. Additionally, Sal also reduces the levels of serum biochemical markers (serum creatinine, Scr; blood urea nitrogen, BUN; and uric acid, UA) and decreases the release of inflammatory cytokines (IL-1β, IL-6, TNF-α). Further study revealed that the effect of Sal on renal interstitial fibrosis is associated with the lower expression of TLR4, p-IκBα, p-NF-κB and mitogen-activated protein kinases (MAPK), both in vivo and in vitro. In conclusion, Sal treatment improves kidney function, ameliorates the deposition of the ECM components and relieves the protein levels of EMT markers in mouse kidneys and HK-2 cells. Furthermore, Sal treatment significantly decreases the release of inflammatory cytokines and inhibits the TLR4/NF-κB and MAPK signaling pathways. Collectively, these results suggest that the administration of Sal could be a novel therapeutic strategy in treating renal fibrosis.

Dataset Information

Rhein inhibits malignant phenotypes of human renal cell carcinoma by impacting on MAPK/NF-?B signaling pathways.

Publications

Rhein inhibits malignant phenotypes of human renal cell carcinoma by impacting on MAPK/NF-κB signaling pathways.

Similar Datasets

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