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10.1038/bjc.2014.422 http://scihub22266oqcxt.onion/10.1038/bjc.2014.422 C4183851!4183851 !25101566     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=25101566 &cmd=llinks): Failed to open stream: HTTP request failed! 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Negative regulation of signal transducer and activator of transcription-3 signalling cascade by lupeol inhibits growth and induces apoptosis in hepatocellular carcinoma cells |pdf=|usr=}}{{25101566 }} gab.com Text Negative regulation of signal transducer and activator of transcription-3 signalling cascade by lupeol inhibits growth and induces apoptosis in hepatocellular carcinoma cells JO: Br J Cancer http://www.kidney.de/pget.php?&tw=1&pmid=25101566 #FOAvip BACKGROUND: Constitutive activation of signal transducer and activator of transcription signalling 3 (STAT3) has been linked with survival, proliferation and angiogenesis in a wide variety of malignancies including hepatocellular carcinoma (HCC). METHODS: We evaluated the effect of lupeol on STAT3 signalling cascade and its regulated functional responses in HCC cells. RESULTS: Lupeol suppressed constitutive activation of STAT3 phosphorylation at tyrosine 705 residue effectively in a dose- and time-dependent manner. The phosphorylation of Janus-activated kinases (JAKs) 1 and 2 and Src was also suppressed by lupeol. Pervanadate treatment reversed the downregulation of phospho-STAT3 induced by lupeol, thereby indicating the involvement of a phosphatase. Indeed, we observed that treatment with lupeol increased the protein and mRNA levels of SHP-2, and silencing of SHP-2 abolished the inhibitory effects of lupeol on STAT3 activation. Treatment with lupeol also downregulated the expression of diverse STAT3-regulated genes and decreased the binding of STAT3 to VEGF promoter. Moreover, the proliferation of various HCC cells was significantly suppressed by lupeol, being associated with substantial induction of apoptosis. Depletion of SHP-2 reversed the observed antiproliferative and pro-apoptotic effects of lupeol. CONCLUSIONS: Lupeol exhibited its potential anticancer effects in HCC through the downregulation of STAT3-induced pro-survival signalling cascade. Twit Text FOAVip Negative regulation of signal transducer and activator of transcription-3 signalling cascade by lupeol inhibits growth and induces apoptosis in hepatocellular carcinoma cells ????Br J Cancer http://www.kidney.de/pget.php?&tw=1&pmid=25101566 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=25101566 #FOAvip English Wikipedia <ref>{{Cite pmid|25101566 }}</ref> Negative regulation of signal transducer and activator of transcription-3 signalling cascade by lupeol inhibits growth and induces apoptosis in hepatocellular carcinoma cells #MMPMID25101566 Siveen KS ; Nguyen AH ; Lee JH ; Li F ; Singh SS ; Kumar AP ; Low G ; Jha S ; Tergaonkar V ; Ahn KS ; Sethi G Br J Cancer 2014[Sep]; 111 (7 ): 1327-37 PMID25101566 show ga BACKGROUND: Constitutive activation of signal transducer and activator of transcription signalling 3 (STAT3) has been linked with survival, proliferation and angiogenesis in a wide variety of malignancies including hepatocellular carcinoma (HCC). METHODS: We evaluated the effect of lupeol on STAT3 signalling cascade and its regulated functional responses in HCC cells. RESULTS: Lupeol suppressed constitutive activation of STAT3 phosphorylation at tyrosine 705 residue effectively in a dose- and time-dependent manner. The phosphorylation of Janus-activated kinases (JAKs) 1 and 2 and Src was also suppressed by lupeol. Pervanadate treatment reversed the downregulation of phospho-STAT3 induced by lupeol, thereby indicating the involvement of a phosphatase. Indeed, we observed that treatment with lupeol increased the protein and mRNA levels of SHP-2, and silencing of SHP-2 abolished the inhibitory effects of lupeol on STAT3 activation. Treatment with lupeol also downregulated the expression of diverse STAT3-regulated genes and decreased the binding of STAT3 to VEGF promoter. Moreover, the proliferation of various HCC cells was significantly suppressed by lupeol, being associated with substantial induction of apoptosis. Depletion of SHP-2 reversed the observed antiproliferative and pro-apoptotic effects of lupeol. CONCLUSIONS: Lupeol exhibited its potential anticancer effects in HCC through the downregulation of STAT3-induced pro-survival signalling cascade. |Antineoplastic Agents/*pharmacology [MESH] |Apoptosis Regulatory Proteins/genetics/metabolism [MESH] |Apoptosis/*drug effects [MESH] |Carcinoma, Hepatocellular [MESH] |Cell Movement [MESH] |Cell Proliferation/drug effects [MESH] |Chemokine CXCL12/physiology [MESH] |Epidermal Growth Factor/physiology [MESH] |Gene Expression Regulation, Neoplastic [MESH] |Hep G2 Cells [MESH] |Humans [MESH] |Janus Kinase 1/genetics/metabolism [MESH] |Janus Kinase 2/genetics/metabolism [MESH] |Liver Neoplasms [MESH] |Pentacyclic Triterpenes/*pharmacology [MESH] |Phosphorylation [MESH] |Promoter Regions, Genetic [MESH] |Protein Binding [MESH] |Protein Processing, Post-Translational/drug effects [MESH] |STAT3 Transcription Factor/*metabolism [MESH] |Signal Transduction/*drug effects [MESH] |Transcriptional Activation [MESH]Negative regulation of signal transducer and activator of transcriptio(epmc).pdf DeepDyve Pubget Overpricing