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XZH-5 Inhibits STAT3 Phosphorylation and Enhances the Cytotoxicity of Chemotherapeutic Drugs in Human Breast and Pancreatic Cancer Cells
Constitutive activation of Signal Transducers and Activators of Transcription 3 (STAT3) signaling is frequently detected in breast and pancreatic cancer. Inhibiting constitutive STAT3 signaling represents a promising molecular target for therapeutic approach. Using structure-based design, we develop...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3463519/ https://www.ncbi.nlm.nih.gov/pubmed/23056374 http://dx.doi.org/10.1371/journal.pone.0046624 |
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author | Liu, Aiguo Liu, Yan Jin, Zhigang Hu, Qun Lin, Li Jou, David Yang, Jing Xu, Zhenghu Wang, Hong Li, Chenglong Lin, Jiayuh |
author_facet | Liu, Aiguo Liu, Yan Jin, Zhigang Hu, Qun Lin, Li Jou, David Yang, Jing Xu, Zhenghu Wang, Hong Li, Chenglong Lin, Jiayuh |
author_sort | Liu, Aiguo |
collection | PubMed |
description | Constitutive activation of Signal Transducers and Activators of Transcription 3 (STAT3) signaling is frequently detected in breast and pancreatic cancer. Inhibiting constitutive STAT3 signaling represents a promising molecular target for therapeutic approach. Using structure-based design, we developed a non-peptide cell-permeable, small molecule, termed as XZH-5, which targeted STAT3 phosphorylation. XZH-5 was found to inhibit STAT3 phosphorylation (Tyr705) and induce apoptosis in human breast and pancreatic cancer cell lines expressing elevated levels of phosphorylated STAT3. XZH-5 could also inhibit interleukin-6-induced STAT3 phosphorylation in cancer cell lines expressing low phosphorylated STAT3. Inhibition of STAT3 signaling by XZH-5 was confirmed by the down-regulation of downstream targets of STAT3, such as Cyclin D1, Bcl-2, and Survivin at mRNA level. In addition, XZH-5 inhibited colony formation, cell migration, and enhanced the cytotoxicity of chemotherapeutic drugs when combined with Doxorubicin or Gemcitabine. Our results indicate that XZH-5 may be a potential therapeutic agent for breast and pancreatic cancers with constitutive STAT3 signaling. |
format | Online Article Text |
id | pubmed-3463519 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-34635192012-10-09 XZH-5 Inhibits STAT3 Phosphorylation and Enhances the Cytotoxicity of Chemotherapeutic Drugs in Human Breast and Pancreatic Cancer Cells Liu, Aiguo Liu, Yan Jin, Zhigang Hu, Qun Lin, Li Jou, David Yang, Jing Xu, Zhenghu Wang, Hong Li, Chenglong Lin, Jiayuh PLoS One Research Article Constitutive activation of Signal Transducers and Activators of Transcription 3 (STAT3) signaling is frequently detected in breast and pancreatic cancer. Inhibiting constitutive STAT3 signaling represents a promising molecular target for therapeutic approach. Using structure-based design, we developed a non-peptide cell-permeable, small molecule, termed as XZH-5, which targeted STAT3 phosphorylation. XZH-5 was found to inhibit STAT3 phosphorylation (Tyr705) and induce apoptosis in human breast and pancreatic cancer cell lines expressing elevated levels of phosphorylated STAT3. XZH-5 could also inhibit interleukin-6-induced STAT3 phosphorylation in cancer cell lines expressing low phosphorylated STAT3. Inhibition of STAT3 signaling by XZH-5 was confirmed by the down-regulation of downstream targets of STAT3, such as Cyclin D1, Bcl-2, and Survivin at mRNA level. In addition, XZH-5 inhibited colony formation, cell migration, and enhanced the cytotoxicity of chemotherapeutic drugs when combined with Doxorubicin or Gemcitabine. Our results indicate that XZH-5 may be a potential therapeutic agent for breast and pancreatic cancers with constitutive STAT3 signaling. Public Library of Science 2012-10-03 /pmc/articles/PMC3463519/ /pubmed/23056374 http://dx.doi.org/10.1371/journal.pone.0046624 Text en © 2012 Liu 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 Liu, Aiguo Liu, Yan Jin, Zhigang Hu, Qun Lin, Li Jou, David Yang, Jing Xu, Zhenghu Wang, Hong Li, Chenglong Lin, Jiayuh XZH-5 Inhibits STAT3 Phosphorylation and Enhances the Cytotoxicity of Chemotherapeutic Drugs in Human Breast and Pancreatic Cancer Cells |
title | XZH-5 Inhibits STAT3 Phosphorylation and Enhances the Cytotoxicity of Chemotherapeutic Drugs in Human Breast and Pancreatic Cancer Cells |
title_full | XZH-5 Inhibits STAT3 Phosphorylation and Enhances the Cytotoxicity of Chemotherapeutic Drugs in Human Breast and Pancreatic Cancer Cells |
title_fullStr | XZH-5 Inhibits STAT3 Phosphorylation and Enhances the Cytotoxicity of Chemotherapeutic Drugs in Human Breast and Pancreatic Cancer Cells |
title_full_unstemmed | XZH-5 Inhibits STAT3 Phosphorylation and Enhances the Cytotoxicity of Chemotherapeutic Drugs in Human Breast and Pancreatic Cancer Cells |
title_short | XZH-5 Inhibits STAT3 Phosphorylation and Enhances the Cytotoxicity of Chemotherapeutic Drugs in Human Breast and Pancreatic Cancer Cells |
title_sort | xzh-5 inhibits stat3 phosphorylation and enhances the cytotoxicity of chemotherapeutic drugs in human breast and pancreatic cancer cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3463519/ https://www.ncbi.nlm.nih.gov/pubmed/23056374 http://dx.doi.org/10.1371/journal.pone.0046624 |
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