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Autophagy activated by the c-Jun N-terminal kinase-mediated pathway protects human prostate cancer PC3 cells from celecoxib-induced apoptosis
The aim of the present study was to investigate the role of autophagy in celecoxib-induced apoptosis in human hormone-insensitive prostate cancer cell line PC3 cells and to explore the underlying molecular mechanism leading to autophagic activation. A cell viability assay was applied to investigate...
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/PMC5443255/ https://www.ncbi.nlm.nih.gov/pubmed/28565848 http://dx.doi.org/10.3892/etm.2017.4287 |
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author | Zhu, Xin Zhou, Mi Liu, Guanyu Huang, Xiaolong He, Weiyang Gou, Xin Jiang, Tao |
author_facet | Zhu, Xin Zhou, Mi Liu, Guanyu Huang, Xiaolong He, Weiyang Gou, Xin Jiang, Tao |
author_sort | Zhu, Xin |
collection | PubMed |
description | The aim of the present study was to investigate the role of autophagy in celecoxib-induced apoptosis in human hormone-insensitive prostate cancer cell line PC3 cells and to explore the underlying molecular mechanism leading to autophagic activation. A cell viability assay was applied to investigate the effect of various concentrations of celecoxib (0, 40, 60, 80, 100 and 120 µmol/l) on PC3 cells for 24 and 48 h, respectively. The 50% inhibitory concentration of celecoxib for 24 h was chosen for subsequent experiments. Annexin V-fluorescein isothiocyanate/propidium iodide double staining flow cytometry, as well as caspase 3 and poly (ADP-ribose) polymerase proteins detected by western blotting, were applied to analyze cellular apoptosis induced by celecoxib. Ultrastructural cellular changes observed by transmission electron microscopy and the level of LC-3 II and P62 detected by western blotting were used to determine the activation of autophagy. It was demonstrated that celecoxib induced apoptosis and activated autophagy in PC3 cells in a dose- and time-dependent manner. Furthermore, flow cytometry and western blotting were applied to elucidate whether the role of autophagy in celecoxib-induced apoptosis is protective or destructive. Blockade of autophagy markedly increased apoptosis, suggesting that celecoxib-activated autophagy was cytoprotective. Additionally, c-jun-N-terminal kinase (JNK) was demonstrated to have a role in autophagic activation, and suppression of JNK was able to reduce autophagy and increase apoptosis. In conclusion, the results of the present study indicate that celecoxib induces apoptosis in PC3 cells; however, celecoxib also activates JNK-mediated autophagy, which exerts cytoprotective effects in prostate cancer PC3 cells. Blockade of autophagy via the JNK-mediated pathway may provide a promising strategy for prostate cancer therapy. |
format | Online Article Text |
id | pubmed-5443255 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-54432552017-05-30 Autophagy activated by the c-Jun N-terminal kinase-mediated pathway protects human prostate cancer PC3 cells from celecoxib-induced apoptosis Zhu, Xin Zhou, Mi Liu, Guanyu Huang, Xiaolong He, Weiyang Gou, Xin Jiang, Tao Exp Ther Med Articles The aim of the present study was to investigate the role of autophagy in celecoxib-induced apoptosis in human hormone-insensitive prostate cancer cell line PC3 cells and to explore the underlying molecular mechanism leading to autophagic activation. A cell viability assay was applied to investigate the effect of various concentrations of celecoxib (0, 40, 60, 80, 100 and 120 µmol/l) on PC3 cells for 24 and 48 h, respectively. The 50% inhibitory concentration of celecoxib for 24 h was chosen for subsequent experiments. Annexin V-fluorescein isothiocyanate/propidium iodide double staining flow cytometry, as well as caspase 3 and poly (ADP-ribose) polymerase proteins detected by western blotting, were applied to analyze cellular apoptosis induced by celecoxib. Ultrastructural cellular changes observed by transmission electron microscopy and the level of LC-3 II and P62 detected by western blotting were used to determine the activation of autophagy. It was demonstrated that celecoxib induced apoptosis and activated autophagy in PC3 cells in a dose- and time-dependent manner. Furthermore, flow cytometry and western blotting were applied to elucidate whether the role of autophagy in celecoxib-induced apoptosis is protective or destructive. Blockade of autophagy markedly increased apoptosis, suggesting that celecoxib-activated autophagy was cytoprotective. Additionally, c-jun-N-terminal kinase (JNK) was demonstrated to have a role in autophagic activation, and suppression of JNK was able to reduce autophagy and increase apoptosis. In conclusion, the results of the present study indicate that celecoxib induces apoptosis in PC3 cells; however, celecoxib also activates JNK-mediated autophagy, which exerts cytoprotective effects in prostate cancer PC3 cells. Blockade of autophagy via the JNK-mediated pathway may provide a promising strategy for prostate cancer therapy. D.A. Spandidos 2017-05 2017-03-30 /pmc/articles/PMC5443255/ /pubmed/28565848 http://dx.doi.org/10.3892/etm.2017.4287 Text en Copyright: © Zhu 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 Zhu, Xin Zhou, Mi Liu, Guanyu Huang, Xiaolong He, Weiyang Gou, Xin Jiang, Tao Autophagy activated by the c-Jun N-terminal kinase-mediated pathway protects human prostate cancer PC3 cells from celecoxib-induced apoptosis |
title | Autophagy activated by the c-Jun N-terminal kinase-mediated pathway protects human prostate cancer PC3 cells from celecoxib-induced apoptosis |
title_full | Autophagy activated by the c-Jun N-terminal kinase-mediated pathway protects human prostate cancer PC3 cells from celecoxib-induced apoptosis |
title_fullStr | Autophagy activated by the c-Jun N-terminal kinase-mediated pathway protects human prostate cancer PC3 cells from celecoxib-induced apoptosis |
title_full_unstemmed | Autophagy activated by the c-Jun N-terminal kinase-mediated pathway protects human prostate cancer PC3 cells from celecoxib-induced apoptosis |
title_short | Autophagy activated by the c-Jun N-terminal kinase-mediated pathway protects human prostate cancer PC3 cells from celecoxib-induced apoptosis |
title_sort | autophagy activated by the c-jun n-terminal kinase-mediated pathway protects human prostate cancer pc3 cells from celecoxib-induced apoptosis |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5443255/ https://www.ncbi.nlm.nih.gov/pubmed/28565848 http://dx.doi.org/10.3892/etm.2017.4287 |
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