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Icaritin Inhibits JAK/STAT3 Signaling and Growth of Renal Cell Carcinoma
Signal transducer and activator of transcription-3 (STAT3) is critical for cancer progression by regulating tumor cell survival, proliferation, and angiogenesis. Herein, we investigated the regulation of STAT3 activation and the therapeutic effects of Icaritin, a prenyl flavonoid derivative from Epi...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3855768/ https://www.ncbi.nlm.nih.gov/pubmed/24324713 http://dx.doi.org/10.1371/journal.pone.0081657 |
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author | Li, Shasha Priceman, Saul J. Xin, Hong Zhang, Wang Deng, Jiehui Liu, Yong Huang, Jiabin Zhu, Wenshan Chen, Mingjie Hu, Wei Deng, Xiaomin Zhang, Jian Yu, Hua He, Guangyuan |
author_facet | Li, Shasha Priceman, Saul J. Xin, Hong Zhang, Wang Deng, Jiehui Liu, Yong Huang, Jiabin Zhu, Wenshan Chen, Mingjie Hu, Wei Deng, Xiaomin Zhang, Jian Yu, Hua He, Guangyuan |
author_sort | Li, Shasha |
collection | PubMed |
description | Signal transducer and activator of transcription-3 (STAT3) is critical for cancer progression by regulating tumor cell survival, proliferation, and angiogenesis. Herein, we investigated the regulation of STAT3 activation and the therapeutic effects of Icaritin, a prenyl flavonoid derivative from Epimedium Genus, in renal cell carcinoma (RCC). Icaritin showed significant anti-tumor activity in the human and mouse RCC cell lines, 786-O and Renca, respectively. Icaritin inhibited both constitutive and IL-6-induced phospho-STAT3 (STAT3(Y705)) and reduced the level of STAT3-regulated proteins Bcl-xL, Mcl-1, Survivin, and CyclinD1 in a dose-dependent manner. Icaritin also inhibited activation of Janus-activated kinase-2 (JAK2), while it showed minimal effects on the activation of other key signaling pathways, including AKT and MAPK. Expression of the constitutively active form of STAT3 blocked Icaritin-induced apoptosis, while siRNA directed against STAT3 potentiated apoptosis. Finally, Icaritin significantly blunted RCC tumor growth in vivo, reduced STAT3 activation, and inhibited Bcl-xL and Cyclin E, as well as VEGF expression in tumors, which was associated with reduced tumor angiogenesis. Overall, these results suggest that Icaritin strongly inhibits STAT3 activation and is a potentially effective therapeutic option for the treatment of renal cell carcinoma. |
format | Online Article Text |
id | pubmed-3855768 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-38557682013-12-09 Icaritin Inhibits JAK/STAT3 Signaling and Growth of Renal Cell Carcinoma Li, Shasha Priceman, Saul J. Xin, Hong Zhang, Wang Deng, Jiehui Liu, Yong Huang, Jiabin Zhu, Wenshan Chen, Mingjie Hu, Wei Deng, Xiaomin Zhang, Jian Yu, Hua He, Guangyuan PLoS One Research Article Signal transducer and activator of transcription-3 (STAT3) is critical for cancer progression by regulating tumor cell survival, proliferation, and angiogenesis. Herein, we investigated the regulation of STAT3 activation and the therapeutic effects of Icaritin, a prenyl flavonoid derivative from Epimedium Genus, in renal cell carcinoma (RCC). Icaritin showed significant anti-tumor activity in the human and mouse RCC cell lines, 786-O and Renca, respectively. Icaritin inhibited both constitutive and IL-6-induced phospho-STAT3 (STAT3(Y705)) and reduced the level of STAT3-regulated proteins Bcl-xL, Mcl-1, Survivin, and CyclinD1 in a dose-dependent manner. Icaritin also inhibited activation of Janus-activated kinase-2 (JAK2), while it showed minimal effects on the activation of other key signaling pathways, including AKT and MAPK. Expression of the constitutively active form of STAT3 blocked Icaritin-induced apoptosis, while siRNA directed against STAT3 potentiated apoptosis. Finally, Icaritin significantly blunted RCC tumor growth in vivo, reduced STAT3 activation, and inhibited Bcl-xL and Cyclin E, as well as VEGF expression in tumors, which was associated with reduced tumor angiogenesis. Overall, these results suggest that Icaritin strongly inhibits STAT3 activation and is a potentially effective therapeutic option for the treatment of renal cell carcinoma. Public Library of Science 2013-12-06 /pmc/articles/PMC3855768/ /pubmed/24324713 http://dx.doi.org/10.1371/journal.pone.0081657 Text en © 2013 Li et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Li, Shasha Priceman, Saul J. Xin, Hong Zhang, Wang Deng, Jiehui Liu, Yong Huang, Jiabin Zhu, Wenshan Chen, Mingjie Hu, Wei Deng, Xiaomin Zhang, Jian Yu, Hua He, Guangyuan Icaritin Inhibits JAK/STAT3 Signaling and Growth of Renal Cell Carcinoma |
title | Icaritin Inhibits JAK/STAT3 Signaling and Growth of Renal Cell Carcinoma |
title_full | Icaritin Inhibits JAK/STAT3 Signaling and Growth of Renal Cell Carcinoma |
title_fullStr | Icaritin Inhibits JAK/STAT3 Signaling and Growth of Renal Cell Carcinoma |
title_full_unstemmed | Icaritin Inhibits JAK/STAT3 Signaling and Growth of Renal Cell Carcinoma |
title_short | Icaritin Inhibits JAK/STAT3 Signaling and Growth of Renal Cell Carcinoma |
title_sort | icaritin inhibits jak/stat3 signaling and growth of renal cell carcinoma |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3855768/ https://www.ncbi.nlm.nih.gov/pubmed/24324713 http://dx.doi.org/10.1371/journal.pone.0081657 |
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