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10.1038/onc.2014.72 http://scihub22266oqcxt.onion/10.1038/onc.2014.72 C4182178!4182178 !24681959     free     free     free Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 235.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 269.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 269.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 269.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 269.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 269.2 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\24681959 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Oncogene 2015 ; 34 (11 ): 1341-53 Nephropedia Template TP {{tp|p=24681959 |t=2015. Drug-repositioning screening identified piperlongumine as a direct STAT3 inhibitor with potent activity against breast cancer |pdf=|usr=}}{{24681959 }} gab.com Text Drug-repositioning screening identified piperlongumine as a direct STAT3 inhibitor with potent activity against breast cancer JO: Oncogene http://www.kidney.de/pget.php?&tw=1&pmid=24681959 #FOAvip Signal transducer and activator of transcription (STAT) 3 regulates many cardinal features of cancer including cancer cell growth, apoptosis resistance, DNA damage response, metastasis, immune escape, tumor angiogenesis, the Warburg effect and oncogene addiction and has been validated as a drug target for cancer therapy. Several strategies have been used to identify agents that target Stat3 in breast cancer but none has yet entered into clinical use. We used a high-throughput fluorescence microscopy search strategy to identify compounds in a drug-repositioning library (Prestwick library) that block ligand-induced nuclear translocation of Stat3 and identified piperlongumine (PL), a natural product isolated from the fruit of the pepper Piper longum. PL inhibited Stat3 nuclear translocation, inhibited ligand-induced and constitutive Stat3 phosphorylation, and modulated expression of multiple Stat3-regulated genes. Surface plasmon resonance assay revealed that PL directly inhibited binding of Stat3 to its phosphotyrosyl peptide ligand. Phosphoprotein antibody array analysis revealed that PL does not modulate kinases known to activate Stat3 such as Janus kinases, Src kinase family members or receptor tyrosine kinases. PL inhibited anchorage-independent and anchorage-dependent growth of multiple breast cancer cell lines having increased pStat3 or total Stat3, and induced apoptosis. PL also inhibited mammosphere formation by tumor cells from patient-derived xenografts. PL's antitumorigenic function was causally linked to its Stat3-inhibitory effect. PL was non-toxic in mice up to a dose of 30?mg/kg/day for 14 days and caused regression of breast cancer cell line xenografts in nude mice. Thus, PL represents a promising new agent for rapid entry into the clinic for use in treating breast cancer, as well as other cancers in which Stat3 has a role. Twit Text FOAVip Drug-repositioning screening identified piperlongumine as a direct STAT3 inhibitor with potent activity against breast cancer ????Oncogene http://www.kidney.de/pget.php?&tw=1&pmid=24681959 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=24681959 #FOAvip English Wikipedia <ref>{{Cite pmid|24681959 }}</ref> Drug-repositioning screening identified piperlongumine as a direct STAT3 inhibitor with potent activity against breast cancer #MMPMID24681959 Bharadwaj U ; Eckols TK ; Kolosov M ; Kasembeli MM ; Adam A ; Torres D ; Zhang X ; Dobrolecki LE ; Wei W ; Lewis MT ; Dave B ; Chang JC ; Landis MD ; Creighton CJ ; Mancini MA ; Tweardy DJ Oncogene 2015[Mar]; 34 (11 ): 1341-53 PMID24681959 show ga Signal transducer and activator of transcription (STAT) 3 regulates many cardinal features of cancer including cancer cell growth, apoptosis resistance, DNA damage response, metastasis, immune escape, tumor angiogenesis, the Warburg effect and oncogene addiction and has been validated as a drug target for cancer therapy. Several strategies have been used to identify agents that target Stat3 in breast cancer but none has yet entered into clinical use. We used a high-throughput fluorescence microscopy search strategy to identify compounds in a drug-repositioning library (Prestwick library) that block ligand-induced nuclear translocation of Stat3 and identified piperlongumine (PL), a natural product isolated from the fruit of the pepper Piper longum. PL inhibited Stat3 nuclear translocation, inhibited ligand-induced and constitutive Stat3 phosphorylation, and modulated expression of multiple Stat3-regulated genes. Surface plasmon resonance assay revealed that PL directly inhibited binding of Stat3 to its phosphotyrosyl peptide ligand. Phosphoprotein antibody array analysis revealed that PL does not modulate kinases known to activate Stat3 such as Janus kinases, Src kinase family members or receptor tyrosine kinases. PL inhibited anchorage-independent and anchorage-dependent growth of multiple breast cancer cell lines having increased pStat3 or total Stat3, and induced apoptosis. PL also inhibited mammosphere formation by tumor cells from patient-derived xenografts. PL's antitumorigenic function was causally linked to its Stat3-inhibitory effect. PL was non-toxic in mice up to a dose of 30?mg/kg/day for 14 days and caused regression of breast cancer cell line xenografts in nude mice. Thus, PL represents a promising new agent for rapid entry into the clinic for use in treating breast cancer, as well as other cancers in which Stat3 has a role. |*Drug Repositioning [MESH] |Active Transport, Cell Nucleus/drug effects [MESH] |Animals [MESH] |Antineoplastic Agents/adverse effects/*pharmacology/therapeutic use [MESH] |Apoptosis/drug effects [MESH] |Breast Neoplasms/*drug therapy [MESH] |Cell Proliferation/drug effects [MESH] |Dioxolanes/adverse effects/*pharmacology/therapeutic use [MESH] |Female [MESH] |Gene Expression/drug effects [MESH] |Humans [MESH] |MCF-7 Cells [MESH] |Mice [MESH] |Mice, Nude [MESH] |Mice, SCID [MESH] |Neoplasm Transplantation [MESH] |Oxidative Stress/drug effects [MESH] |Phosphorylation/drug effects [MESH] |Reverse Transcriptase Polymerase Chain Reaction [MESH] |STAT3 Transcription Factor/*antagonists & inhibitors/genetics/metabolism [MESH] |Signal Transduction/drug effects [MESH] |Spheroids, Cellular/drug effects [MESH] |Surface Plasmon Resonance [MESH] |Transplantation, Heterologous [MESH]Drug-repositioning screening identified piperlongumine as a direct STA(epmc).pdf DeepDyve Pubget Overpricing