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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...

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Autores principales: Zhao, Xiaofeng, Huang, Lu, Xu, Wanwan, Chen, Xiaoyan, Shen, Yan, Zeng, Wenjie, Chen, Xiao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
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.
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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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