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Physapubescin B inhibits tumorgenesis and circumvents taxol resistance of ovarian cancer cells through STAT3 signaling
Ovarian cancer is the most lethal gynaecological malignancy. Recurrence and subsequent resistance to chemotherapy have become major obstacles to treating these diseases. In the present study, we showed that a natural withanolide isolated from the plant Physalis pubescens L. (Solanaceae), Physapubesc...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5642541/ https://www.ncbi.nlm.nih.gov/pubmed/29050266 http://dx.doi.org/10.18632/oncotarget.19593 |
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author | Zhao, Xiaofeng Huang, Lu Xu, Wanwan Chen, Xiaoyan Shen, Yan Zeng, Wenjie Chen, Xiao |
author_facet | Zhao, Xiaofeng Huang, Lu Xu, Wanwan Chen, Xiaoyan Shen, Yan Zeng, Wenjie Chen, Xiao |
author_sort | Zhao, Xiaofeng |
collection | PubMed |
description | Ovarian cancer is the most lethal gynaecological malignancy. Recurrence and subsequent resistance to chemotherapy have become major obstacles to treating these diseases. In the present study, we showed that a natural withanolide isolated from the plant Physalis pubescens L. (Solanaceae), Physapubescin B, exhibited potent anti-tumor activity against ovarian cancer cells. Physapubescin B promoted apoptosis, induced cell-cycle arrest and inhibited invasion of ES-2 and A2780 cells. Physapubescin B treatment also resulted in suppression of the transcriptional activity of STAT3, an oncogenic transcription factor activated in many human malignancies including ovarian cancer, through disturbing the dimerization of STAT3, and thereby inhibited the nuclear translocation of Tyr705/Ser727-phosphorylated STAT3. The IL-6-stimulated activation of STAT3 and its downstream genes Cyclin D1, survivin, and Bcl-xL was also repressed by Physapubescin B. Furthermore, Physapubescin B sensitizes A2780 cells to taxol-induced cell growth inhibition in vitro. These findings strongly suggest that Physapubescin B has potential antitumor activity and may circumvent taxol resistance in human ovarian cancer cells through inhibition of aberrant activation of STAT3. |
format | Online Article Text |
id | pubmed-5642541 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-56425412017-10-18 Physapubescin B inhibits tumorgenesis and circumvents taxol resistance of ovarian cancer cells through STAT3 signaling Zhao, Xiaofeng Huang, Lu Xu, Wanwan Chen, Xiaoyan Shen, Yan Zeng, Wenjie Chen, Xiao Oncotarget Research Paper Ovarian cancer is the most lethal gynaecological malignancy. Recurrence and subsequent resistance to chemotherapy have become major obstacles to treating these diseases. In the present study, we showed that a natural withanolide isolated from the plant Physalis pubescens L. (Solanaceae), Physapubescin B, exhibited potent anti-tumor activity against ovarian cancer cells. Physapubescin B promoted apoptosis, induced cell-cycle arrest and inhibited invasion of ES-2 and A2780 cells. Physapubescin B treatment also resulted in suppression of the transcriptional activity of STAT3, an oncogenic transcription factor activated in many human malignancies including ovarian cancer, through disturbing the dimerization of STAT3, and thereby inhibited the nuclear translocation of Tyr705/Ser727-phosphorylated STAT3. The IL-6-stimulated activation of STAT3 and its downstream genes Cyclin D1, survivin, and Bcl-xL was also repressed by Physapubescin B. Furthermore, Physapubescin B sensitizes A2780 cells to taxol-induced cell growth inhibition in vitro. These findings strongly suggest that Physapubescin B has potential antitumor activity and may circumvent taxol resistance in human ovarian cancer cells through inhibition of aberrant activation of STAT3. Impact Journals LLC 2017-07-26 /pmc/articles/PMC5642541/ /pubmed/29050266 http://dx.doi.org/10.18632/oncotarget.19593 Text en Copyright: © 2017 Zhao et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Zhao, Xiaofeng Huang, Lu Xu, Wanwan Chen, Xiaoyan Shen, Yan Zeng, Wenjie Chen, Xiao Physapubescin B inhibits tumorgenesis and circumvents taxol resistance of ovarian cancer cells through STAT3 signaling |
title | Physapubescin B inhibits tumorgenesis and circumvents taxol resistance of ovarian cancer cells through STAT3 signaling |
title_full | Physapubescin B inhibits tumorgenesis and circumvents taxol resistance of ovarian cancer cells through STAT3 signaling |
title_fullStr | Physapubescin B inhibits tumorgenesis and circumvents taxol resistance of ovarian cancer cells through STAT3 signaling |
title_full_unstemmed | Physapubescin B inhibits tumorgenesis and circumvents taxol resistance of ovarian cancer cells through STAT3 signaling |
title_short | Physapubescin B inhibits tumorgenesis and circumvents taxol resistance of ovarian cancer cells through STAT3 signaling |
title_sort | physapubescin b inhibits tumorgenesis and circumvents taxol resistance of ovarian cancer cells through stat3 signaling |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5642541/ https://www.ncbi.nlm.nih.gov/pubmed/29050266 http://dx.doi.org/10.18632/oncotarget.19593 |
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