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10.1038/bjc.2013.285 http://scihub22266oqcxt.onion/10.1038/bjc.2013.285 23756865!3708553!23756865     free     free     free Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 243.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 276.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 276.79999999999995 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Br+J+Cancer 2013 ; 109 (1): 83-91 Nephropedia Template TP {{tp|p=23756865|t=2013. Inhibition of VEGF expression through blockade of Hif1alpha and STAT3 signalling mediates the anti-angiogenic effect of melatonin in HepG2 liver cancer cells |pdf=|usr=}}{{23756865}} gab.com Text Inhibition of VEGF expression through blockade of Hif1alpha and STAT3 signalling mediates the anti-angiogenic effect of melatonin in HepG2 liver cancer cells JO: Br J Cancer http://www.kidney.de/pget.php?&tw=1&pmid=23756865 #FOAvip BACKGROUND: Hepatocellular carcinoma (HCC) growth relies on angiogenesis via vascular endothelial growth factor (VEGF) release. Hypoxia within tumour environment leads to intracellular stabilisation of hypoxia inducible factor 1 alpha (Hif1alpha) and signal transducer and activator of transcription (STAT3). Melatonin induces apoptosis in HCC, and shows anti-angiogenic features in several tumours. In this study, we used human HepG2 liver cancer cells as an in vitro model to investigate the anti-angiogenic effects of melatonin. METHODS: HepG2 cells were treated with melatonin under normoxic or CoCl2-induced hypoxia. Gene expression was analysed by RT-qPCR and western blot. Melatonin-induced anti-angiogenic activity was confirmed by in vivo human umbilical vein endothelial cells (HUVECs) tube formation assay. Secreted VEGF was measured by ELISA. Immunofluorescence was performed to analyse Hif1alpha cellular localisation. Physical interaction between Hif1alpha and its co-activators was analysed by immunoprecipitation and chromatin immunoprecipitation (ChIP). RESULTS: Melatonin at a pharmacological concentration (1 mM) decreases cellular and secreted VEGF levels, and prevents HUVECs tube formation under hypoxia, associated with a reduction in Hif1alpha protein expression, nuclear localisation, and transcriptional activity. While hypoxia increases phospho-STAT3, Hif1alpha, and CBP/p300 recruitment as a transcriptional complex within the VEGF promoter, melatonin 1 mM decreases their physical interaction. Melatonin and the selective STAT3 inhibitor Stattic show a synergic effect on Hif1alpha, STAT3, and VEGF expression. CONCLUSION: Melatonin exerts an anti-angiogenic activity in HepG2 cells by interfering with the transcriptional activation of VEGF, via Hif1alpha and STAT3. Our results provide evidence to consider this indole as a powerful anti-angiogenic agent for HCC treatment. Twit Text FOAVip Inhibition of VEGF expression through blockade of Hif1alpha and STAT3 signalling mediates the anti-angiogenic effect of melatonin in HepG2 liver cancer cells ????Br J Cancer http://www.kidney.de/pget.php?&tw=1&pmid=23756865 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=23756865 #FOAvip English Wikipedia <ref>{{Cite pmid|23756865}}</ref> Inhibition of VEGF expression through blockade of Hif1alpha and STAT3 signalling mediates the anti-angiogenic effect of melatonin in HepG2 liver cancer cells #MMPMID23756865 Carbajo-Pescador S; Ordonez R; Benet M; Jover R; Garcia-Palomo A; Mauriz JL; Gonzalez-Gallego J Br J Cancer 2013[Jul]; 109 (1): 83-91 PMID23756865show ga BACKGROUND: Hepatocellular carcinoma (HCC) growth relies on angiogenesis via vascular endothelial growth factor (VEGF) release. Hypoxia within tumour environment leads to intracellular stabilisation of hypoxia inducible factor 1 alpha (Hif1alpha) and signal transducer and activator of transcription (STAT3). Melatonin induces apoptosis in HCC, and shows anti-angiogenic features in several tumours. In this study, we used human HepG2 liver cancer cells as an in vitro model to investigate the anti-angiogenic effects of melatonin. METHODS: HepG2 cells were treated with melatonin under normoxic or CoCl2-induced hypoxia. Gene expression was analysed by RT-qPCR and western blot. Melatonin-induced anti-angiogenic activity was confirmed by in vivo human umbilical vein endothelial cells (HUVECs) tube formation assay. Secreted VEGF was measured by ELISA. Immunofluorescence was performed to analyse Hif1alpha cellular localisation. Physical interaction between Hif1alpha and its co-activators was analysed by immunoprecipitation and chromatin immunoprecipitation (ChIP). RESULTS: Melatonin at a pharmacological concentration (1 mM) decreases cellular and secreted VEGF levels, and prevents HUVECs tube formation under hypoxia, associated with a reduction in Hif1alpha protein expression, nuclear localisation, and transcriptional activity. While hypoxia increases phospho-STAT3, Hif1alpha, and CBP/p300 recruitment as a transcriptional complex within the VEGF promoter, melatonin 1 mM decreases their physical interaction. Melatonin and the selective STAT3 inhibitor Stattic show a synergic effect on Hif1alpha, STAT3, and VEGF expression. CONCLUSION: Melatonin exerts an anti-angiogenic activity in HepG2 cells by interfering with the transcriptional activation of VEGF, via Hif1alpha and STAT3. Our results provide evidence to consider this indole as a powerful anti-angiogenic agent for HCC treatment. |Angiogenesis Inhibitors/*pharmacology[MESH] |Apoptosis/drug effects[MESH] |Carcinoma, Hepatocellular/*metabolism[MESH] |Cell Hypoxia[MESH] |Cobalt[MESH] |Cyclic S-Oxides/pharmacology[MESH] |Gene Expression Regulation, Neoplastic[MESH] |Hep G2 Cells[MESH] |Human Umbilical Vein Endothelial Cells[MESH] |Humans[MESH] |Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism[MESH] |Liver Neoplasms/*metabolism[MESH] |Melatonin/*pharmacology[MESH] |Neovascularization, Pathologic/drug therapy[MESH] |Promoter Regions, Genetic[MESH] |STAT3 Transcription Factor/*metabolism[MESH] |Signal Transduction[MESH] |Transcription, Genetic[MESH] |Transcriptional Activation[MESH] |Vascular Endothelial Growth Factor A/biosynthesis/genetics/*metabolism[MESH]Inhibition of VEGF expression through blockade of Hif1alpha and STAT3 (epmc).pdf DeepDyve Pubget Overpricing