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BMH-21 inhibits viability and induces apoptosis by p53-dependent nucleolar stress responses in SKOV3 ovarian cancer cells
The nucleolus is a stress sensor associated with cell cycle progression and apoptosis. Studies have shown that nucleolar stress is positively correlated with apoptosis in breast, prostate and lung cancer cells. However, the role and function of nucleolar stress in ovarian cancer has not been reporte...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5561869/ https://www.ncbi.nlm.nih.gov/pubmed/28656213 http://dx.doi.org/10.3892/or.2017.5750 |
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author | Fu, Xinxu Xu, Lu Qi, Ling Tian, Hongyan Yi, Dan Yu, Yang Liu, Shibing Li, Songyan Xu, Ye Wang, Chunyan |
author_facet | Fu, Xinxu Xu, Lu Qi, Ling Tian, Hongyan Yi, Dan Yu, Yang Liu, Shibing Li, Songyan Xu, Ye Wang, Chunyan |
author_sort | Fu, Xinxu |
collection | PubMed |
description | The nucleolus is a stress sensor associated with cell cycle progression and apoptosis. Studies have shown that nucleolar stress is positively correlated with apoptosis in breast, prostate and lung cancer cells. However, the role and function of nucleolar stress in ovarian cancer has not been reported. In this study, we found that the nucleolar stress inducer BMH-21 inhibited viability of SKOV3 ovarian cancer cells in a dose-dependent manner. Furthermore, BMH-21 induced the expression of nucleolar stress marker proteins (nucleolin, nucleophosmin and fibrillarin) and promoted the nuclear export of these proteins. BMH-21 also decreased MDM2 proto-oncogene expression and increased protein levels of the tumor suppressor p53 and p53 phosphorylated at serine 15 (p-p53-Ser15), which contributed to increased expression of the downstream apoptosis-related protein BCL2 associated X (BAX) and activation of caspase-3. Taken together, these data provide the first reported evidence that induction of p53-dependent nucleolar stress by BMH-21 induces apoptosis in ovarian cancer. Our data suggest that nucleolar stress might be a pathway suitable for targeting in ovarian cancer. |
format | Online Article Text |
id | pubmed-5561869 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-55618692017-11-02 BMH-21 inhibits viability and induces apoptosis by p53-dependent nucleolar stress responses in SKOV3 ovarian cancer cells Fu, Xinxu Xu, Lu Qi, Ling Tian, Hongyan Yi, Dan Yu, Yang Liu, Shibing Li, Songyan Xu, Ye Wang, Chunyan Oncol Rep Articles The nucleolus is a stress sensor associated with cell cycle progression and apoptosis. Studies have shown that nucleolar stress is positively correlated with apoptosis in breast, prostate and lung cancer cells. However, the role and function of nucleolar stress in ovarian cancer has not been reported. In this study, we found that the nucleolar stress inducer BMH-21 inhibited viability of SKOV3 ovarian cancer cells in a dose-dependent manner. Furthermore, BMH-21 induced the expression of nucleolar stress marker proteins (nucleolin, nucleophosmin and fibrillarin) and promoted the nuclear export of these proteins. BMH-21 also decreased MDM2 proto-oncogene expression and increased protein levels of the tumor suppressor p53 and p53 phosphorylated at serine 15 (p-p53-Ser15), which contributed to increased expression of the downstream apoptosis-related protein BCL2 associated X (BAX) and activation of caspase-3. Taken together, these data provide the first reported evidence that induction of p53-dependent nucleolar stress by BMH-21 induces apoptosis in ovarian cancer. Our data suggest that nucleolar stress might be a pathway suitable for targeting in ovarian cancer. D.A. Spandidos 2017-08 2017-06-23 /pmc/articles/PMC5561869/ /pubmed/28656213 http://dx.doi.org/10.3892/or.2017.5750 Text en Copyright: © Fu et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Fu, Xinxu Xu, Lu Qi, Ling Tian, Hongyan Yi, Dan Yu, Yang Liu, Shibing Li, Songyan Xu, Ye Wang, Chunyan BMH-21 inhibits viability and induces apoptosis by p53-dependent nucleolar stress responses in SKOV3 ovarian cancer cells |
title | BMH-21 inhibits viability and induces apoptosis by p53-dependent nucleolar stress responses in SKOV3 ovarian cancer cells |
title_full | BMH-21 inhibits viability and induces apoptosis by p53-dependent nucleolar stress responses in SKOV3 ovarian cancer cells |
title_fullStr | BMH-21 inhibits viability and induces apoptosis by p53-dependent nucleolar stress responses in SKOV3 ovarian cancer cells |
title_full_unstemmed | BMH-21 inhibits viability and induces apoptosis by p53-dependent nucleolar stress responses in SKOV3 ovarian cancer cells |
title_short | BMH-21 inhibits viability and induces apoptosis by p53-dependent nucleolar stress responses in SKOV3 ovarian cancer cells |
title_sort | bmh-21 inhibits viability and induces apoptosis by p53-dependent nucleolar stress responses in skov3 ovarian cancer cells |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5561869/ https://www.ncbi.nlm.nih.gov/pubmed/28656213 http://dx.doi.org/10.3892/or.2017.5750 |
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