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Mitochondrial dysfunction-mediated apoptosis resistance associates with defective heat shock protein response in African–American men with prostate cancer
BACKGROUND: African–American (AA) patients with prostate cancer (PCa) respond poorly to current therapy compared with Caucasian American (CA) PCa patients. Although underlying mechanisms are not defined, mitochondrial dysfunction is a key reason for this disparity. METHODS: Cell death, cell cycle, a...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4865976/ https://www.ncbi.nlm.nih.gov/pubmed/27115471 http://dx.doi.org/10.1038/bjc.2016.88 |
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author | Chaudhary, Ajay K Bhat, Tariq A Kumar, Sandeep Kumar, Anil Kumar, Rahul Underwood, Willie Koochekpour, Shahriar Shourideh, Mojgan Yadav, Neelu Dhar, Shanta Chandra, Dhyan |
author_facet | Chaudhary, Ajay K Bhat, Tariq A Kumar, Sandeep Kumar, Anil Kumar, Rahul Underwood, Willie Koochekpour, Shahriar Shourideh, Mojgan Yadav, Neelu Dhar, Shanta Chandra, Dhyan |
author_sort | Chaudhary, Ajay K |
collection | PubMed |
description | BACKGROUND: African–American (AA) patients with prostate cancer (PCa) respond poorly to current therapy compared with Caucasian American (CA) PCa patients. Although underlying mechanisms are not defined, mitochondrial dysfunction is a key reason for this disparity. METHODS: Cell death, cell cycle, and mitochondrial function/stress were analysed by flow cytometry or by Seahorse XF24 analyzer. Expression of cellular proteins was determined using immunoblotting and real-time PCR analyses. Cell survival/motility was evaluated by clonogenic, cell migration, and gelatin zymography assays. RESULTS: Glycolytic pathway inhibitor dichloroacetate (DCA) inhibited cell proliferation in both AA PCa cells (AA cells) and CA PCa cells (CA cells). AA cells possess reduced endogenous reactive oxygen species, mitochondrial membrane potential (mtMP), and mitochondrial mass compared with CA cells. DCA upregulated mtMP in both cell types, whereas mitochondrial mass was significantly increased in CA cells. DCA enhanced taxol-induced cell death in CA cells while sensitising AA cells to doxorubicin. Reduced expression of heat shock proteins (HSPs) was observed in AA cells, whereas DCA induced expression of CHOP, C/EBP, HSP60, and HSP90 in CA cells. AA cells are more aggressive and metastatic than CA cells. CONCLUSIONS: Restoration of mitochondrial function may provide new option for reducing PCa health disparity among American men. |
format | Online Article Text |
id | pubmed-4865976 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-48659762017-05-10 Mitochondrial dysfunction-mediated apoptosis resistance associates with defective heat shock protein response in African–American men with prostate cancer Chaudhary, Ajay K Bhat, Tariq A Kumar, Sandeep Kumar, Anil Kumar, Rahul Underwood, Willie Koochekpour, Shahriar Shourideh, Mojgan Yadav, Neelu Dhar, Shanta Chandra, Dhyan Br J Cancer Translational Therapeutics BACKGROUND: African–American (AA) patients with prostate cancer (PCa) respond poorly to current therapy compared with Caucasian American (CA) PCa patients. Although underlying mechanisms are not defined, mitochondrial dysfunction is a key reason for this disparity. METHODS: Cell death, cell cycle, and mitochondrial function/stress were analysed by flow cytometry or by Seahorse XF24 analyzer. Expression of cellular proteins was determined using immunoblotting and real-time PCR analyses. Cell survival/motility was evaluated by clonogenic, cell migration, and gelatin zymography assays. RESULTS: Glycolytic pathway inhibitor dichloroacetate (DCA) inhibited cell proliferation in both AA PCa cells (AA cells) and CA PCa cells (CA cells). AA cells possess reduced endogenous reactive oxygen species, mitochondrial membrane potential (mtMP), and mitochondrial mass compared with CA cells. DCA upregulated mtMP in both cell types, whereas mitochondrial mass was significantly increased in CA cells. DCA enhanced taxol-induced cell death in CA cells while sensitising AA cells to doxorubicin. Reduced expression of heat shock proteins (HSPs) was observed in AA cells, whereas DCA induced expression of CHOP, C/EBP, HSP60, and HSP90 in CA cells. AA cells are more aggressive and metastatic than CA cells. CONCLUSIONS: Restoration of mitochondrial function may provide new option for reducing PCa health disparity among American men. Nature Publishing Group 2016-05-10 2016-04-26 /pmc/articles/PMC4865976/ /pubmed/27115471 http://dx.doi.org/10.1038/bjc.2016.88 Text en Copyright © 2016 Cancer Research UK http://creativecommons.org/licenses/by-nc-sa/4.0/ From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/ |
spellingShingle | Translational Therapeutics Chaudhary, Ajay K Bhat, Tariq A Kumar, Sandeep Kumar, Anil Kumar, Rahul Underwood, Willie Koochekpour, Shahriar Shourideh, Mojgan Yadav, Neelu Dhar, Shanta Chandra, Dhyan Mitochondrial dysfunction-mediated apoptosis resistance associates with defective heat shock protein response in African–American men with prostate cancer |
title | Mitochondrial dysfunction-mediated apoptosis resistance associates with defective heat shock protein response in African–American men with prostate cancer |
title_full | Mitochondrial dysfunction-mediated apoptosis resistance associates with defective heat shock protein response in African–American men with prostate cancer |
title_fullStr | Mitochondrial dysfunction-mediated apoptosis resistance associates with defective heat shock protein response in African–American men with prostate cancer |
title_full_unstemmed | Mitochondrial dysfunction-mediated apoptosis resistance associates with defective heat shock protein response in African–American men with prostate cancer |
title_short | Mitochondrial dysfunction-mediated apoptosis resistance associates with defective heat shock protein response in African–American men with prostate cancer |
title_sort | mitochondrial dysfunction-mediated apoptosis resistance associates with defective heat shock protein response in african–american men with prostate cancer |
topic | Translational Therapeutics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4865976/ https://www.ncbi.nlm.nih.gov/pubmed/27115471 http://dx.doi.org/10.1038/bjc.2016.88 |
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