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10.1111/bph.12708 http://scihub22266oqcxt.onion/10.1111/bph.12708 C4243975!4243975 !24697523     free     free     free Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\24697523 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Br+J+Pharmacol 2014 ; 171 (17 ): 4010-25 Nephropedia Template TP {{tp|p=24697523 |t=2014. YC-1 inhibits proliferation of breast cancer cells by down-regulating EZH2 expression via activation of c-Cbl and ERK |pdf=|usr=}}{{24697523 }} gab.com Text YC-1 inhibits proliferation of breast cancer cells by down-regulating EZH2 expression via activation of c-Cbl and ERK JO: Br J Pharmacol http://www.kidney.de/pget.php?&tw=1&pmid=24697523 #FOAvip BACKGROUND AND PURPOSE: YC-1 exhibits potent anticancer activity via numerous actions in many cancer cell lines. Hence, we investigated the in vivo antitumour efficacy of YC-1 in an MDA-MB-468 xenograft model and elucidated the mechanism of down-regulation of enhancer of zeste homology 2 (EZH2) by YC-1 in breast cancer cells. EXPERIMENTAL APPROACH: In YC-1-treated breast cancer cells and tumour specimens from YC-1-treated MDA-MB-468 xenografts, EZH2 expression was analysed by Western blotting. Pharmacological inhibitors and short hairpin RNA-mediated knockdown were applied to identify possible signalling pathways involved in EZH2 down-regulation by YC-1. KEY RESULTS: YC-1 reduced the viability of breast cancer cells and tumour growth in MDA-MB-468 xenografts. In breast cancer cells, YC-1 down-regulated EZH2 expression in a concentration- and time-dependent manner. Depletion of EZH2 reduced the proliferation and susceptibility of breast cancer cells to YC-1-induced apoptosis. EZH2 expression was suppressed in tumour specimens from YC-1-treated MDA-MB-468 xenograft mice. YC-1 enhanced both the degradation rate and ubiquitination of EZH2. The down-regulation of EZH2 by YC-1 was associated with activation of PKA and Src-Raf-ERK-mediated signalling pathways. Furthermore, depletion of Casitas B-lineage lymphoma (c-Cbl), an E3 ubiquitin ligase, abolished YC-1-induced apoptosis and suppression of EZH2. YC-1 rapidly activated c-Cbl to induce signalling associated with ERK and EZH2. CONCLUSION AND IMPLICATIONS: We discovered that YC-1 induces apoptosis and inhibits tumour growth of breast cancer cells via down-regulation of EZH2 by activating c-Cbl and ERK. These data suggest that YC-1 is a potential anticancer drug candidate for triple-negative breast cancer. Twit Text FOAVip YC-1 inhibits proliferation of breast cancer cells by down-regulating EZH2 expression via activation of c-Cbl and ERK ????Br J Pharmacol http://www.kidney.de/pget.php?&tw=1&pmid=24697523 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=24697523 #FOAvip English Wikipedia <ref>{{Cite pmid|24697523 }}</ref> YC-1 inhibits proliferation of breast cancer cells by down-regulating EZH2 expression via activation of c-Cbl and ERK #MMPMID24697523 Chang LC ; Lin HY ; Tsai MT ; Chou RH ; Lee FY ; Teng CM ; Hsieh MT ; Hung HY ; Huang LJ ; Yu YL ; Kuo SC Br J Pharmacol 2014[Sep]; 171 (17 ): 4010-25 PMID24697523 show ga BACKGROUND AND PURPOSE: YC-1 exhibits potent anticancer activity via numerous actions in many cancer cell lines. Hence, we investigated the in vivo antitumour efficacy of YC-1 in an MDA-MB-468 xenograft model and elucidated the mechanism of down-regulation of enhancer of zeste homology 2 (EZH2) by YC-1 in breast cancer cells. EXPERIMENTAL APPROACH: In YC-1-treated breast cancer cells and tumour specimens from YC-1-treated MDA-MB-468 xenografts, EZH2 expression was analysed by Western blotting. Pharmacological inhibitors and short hairpin RNA-mediated knockdown were applied to identify possible signalling pathways involved in EZH2 down-regulation by YC-1. KEY RESULTS: YC-1 reduced the viability of breast cancer cells and tumour growth in MDA-MB-468 xenografts. In breast cancer cells, YC-1 down-regulated EZH2 expression in a concentration- and time-dependent manner. Depletion of EZH2 reduced the proliferation and susceptibility of breast cancer cells to YC-1-induced apoptosis. EZH2 expression was suppressed in tumour specimens from YC-1-treated MDA-MB-468 xenograft mice. YC-1 enhanced both the degradation rate and ubiquitination of EZH2. The down-regulation of EZH2 by YC-1 was associated with activation of PKA and Src-Raf-ERK-mediated signalling pathways. Furthermore, depletion of Casitas B-lineage lymphoma (c-Cbl), an E3 ubiquitin ligase, abolished YC-1-induced apoptosis and suppression of EZH2. YC-1 rapidly activated c-Cbl to induce signalling associated with ERK and EZH2. CONCLUSION AND IMPLICATIONS: We discovered that YC-1 induces apoptosis and inhibits tumour growth of breast cancer cells via down-regulation of EZH2 by activating c-Cbl and ERK. These data suggest that YC-1 is a potential anticancer drug candidate for triple-negative breast cancer. |Animals [MESH] |Antineoplastic Agents/chemistry/*pharmacology [MESH] |Breast Neoplasms/*drug therapy/metabolism/pathology [MESH] |Cell Proliferation/drug effects [MESH] |Cell Survival/drug effects [MESH] |Dose-Response Relationship, Drug [MESH] |Down-Regulation/drug effects [MESH] |Drug Screening Assays, Antitumor [MESH] |Enhancer of Zeste Homolog 2 Protein [MESH] |Enzyme Activation/drug effects [MESH] |Extracellular Signal-Regulated MAP Kinases/*metabolism [MESH] |Female [MESH] |Gene Expression Regulation, Neoplastic/*drug effects [MESH] |Humans [MESH] |Indazoles/chemistry/*pharmacology [MESH] |Mammary Neoplasms, Experimental/drug therapy/metabolism/pathology [MESH] |Mice [MESH] |Polycomb Repressive Complex 2/biosynthesis/*deficiency/genetics [MESH] |Proto-Oncogene Proteins c-cbl/*metabolism [MESH]YC-1 inhibits proliferation of breast cancer cells by down-regulating (epmc).pdf DeepDyve Pubget Overpricing