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Cadmium Induces p53-Dependent Apoptosis in Human Prostate Epithelial Cells
Cadmium, a widespread toxic pollutant of occupational and environmental concern, is a known human carcinogen. The prostate is a potential target for cadmium carcinogenesis, although the underlying mechanisms are still unclear. Furthermore, cadmium may induce cell death by apoptosis in various cell t...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3308998/ https://www.ncbi.nlm.nih.gov/pubmed/22448262 http://dx.doi.org/10.1371/journal.pone.0033647 |
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author | Aimola, Pierpaolo Carmignani, Marco Volpe, Anna Rita Di Benedetto, Altomare Claudio, Luigi Waalkes, Michael P. van Bokhoven, Adrie Tokar, Erik J. Claudio, Pier Paolo |
author_facet | Aimola, Pierpaolo Carmignani, Marco Volpe, Anna Rita Di Benedetto, Altomare Claudio, Luigi Waalkes, Michael P. van Bokhoven, Adrie Tokar, Erik J. Claudio, Pier Paolo |
author_sort | Aimola, Pierpaolo |
collection | PubMed |
description | Cadmium, a widespread toxic pollutant of occupational and environmental concern, is a known human carcinogen. The prostate is a potential target for cadmium carcinogenesis, although the underlying mechanisms are still unclear. Furthermore, cadmium may induce cell death by apoptosis in various cell types, and it has been hypothesized that a key factor in cadmium-induced malignant transformation is acquisition of apoptotic resistance. We investigated the in vitro effects produced by cadmium exposure in normal or tumor cells derived from human prostate epithelium, including RWPE-1 and its cadmium-transformed derivative CTPE, the primary adenocarcinoma 22Rv1 and CWR-R1 cells and LNCaP, PC-3 and DU145 metastatic cancer cell lines. Cells were treated for 24 hours with different concentrations of CdCl(2) and apoptosis, cell cycle distribution and expression of tumor suppressor proteins were analyzed. Subsequently, cellular response to cadmium was evaluated after siRNA-mediated p53 silencing in wild type p53-expressing RWPE-1 and LNCaP cells, and after adenoviral p53 overexpression in p53-deficient DU145 and PC-3 cell lines. The cell lines exhibited different sensitivity to cadmium, and 24-hour exposure to different CdCl(2) concentrations induced dose- and cell type-dependent apoptotic response and inhibition of cell proliferation that correlated with accumulation of functional p53 and overexpression of p21 in wild type p53-expressing cell lines. On the other hand, p53 silencing was able to suppress cadmium-induced apoptosis. Our results demonstrate that cadmium can induce p53-dependent apoptosis in human prostate epithelial cells and suggest p53 mutation as a possible contributing factor for the acquisition of apoptotic resistance in cadmium prostatic carcinogenesis. |
format | Online Article Text |
id | pubmed-3308998 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-33089982012-03-23 Cadmium Induces p53-Dependent Apoptosis in Human Prostate Epithelial Cells Aimola, Pierpaolo Carmignani, Marco Volpe, Anna Rita Di Benedetto, Altomare Claudio, Luigi Waalkes, Michael P. van Bokhoven, Adrie Tokar, Erik J. Claudio, Pier Paolo PLoS One Research Article Cadmium, a widespread toxic pollutant of occupational and environmental concern, is a known human carcinogen. The prostate is a potential target for cadmium carcinogenesis, although the underlying mechanisms are still unclear. Furthermore, cadmium may induce cell death by apoptosis in various cell types, and it has been hypothesized that a key factor in cadmium-induced malignant transformation is acquisition of apoptotic resistance. We investigated the in vitro effects produced by cadmium exposure in normal or tumor cells derived from human prostate epithelium, including RWPE-1 and its cadmium-transformed derivative CTPE, the primary adenocarcinoma 22Rv1 and CWR-R1 cells and LNCaP, PC-3 and DU145 metastatic cancer cell lines. Cells were treated for 24 hours with different concentrations of CdCl(2) and apoptosis, cell cycle distribution and expression of tumor suppressor proteins were analyzed. Subsequently, cellular response to cadmium was evaluated after siRNA-mediated p53 silencing in wild type p53-expressing RWPE-1 and LNCaP cells, and after adenoviral p53 overexpression in p53-deficient DU145 and PC-3 cell lines. The cell lines exhibited different sensitivity to cadmium, and 24-hour exposure to different CdCl(2) concentrations induced dose- and cell type-dependent apoptotic response and inhibition of cell proliferation that correlated with accumulation of functional p53 and overexpression of p21 in wild type p53-expressing cell lines. On the other hand, p53 silencing was able to suppress cadmium-induced apoptosis. Our results demonstrate that cadmium can induce p53-dependent apoptosis in human prostate epithelial cells and suggest p53 mutation as a possible contributing factor for the acquisition of apoptotic resistance in cadmium prostatic carcinogenesis. Public Library of Science 2012-03-20 /pmc/articles/PMC3308998/ /pubmed/22448262 http://dx.doi.org/10.1371/journal.pone.0033647 Text en This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. |
spellingShingle | Research Article Aimola, Pierpaolo Carmignani, Marco Volpe, Anna Rita Di Benedetto, Altomare Claudio, Luigi Waalkes, Michael P. van Bokhoven, Adrie Tokar, Erik J. Claudio, Pier Paolo Cadmium Induces p53-Dependent Apoptosis in Human Prostate Epithelial Cells |
title | Cadmium Induces p53-Dependent Apoptosis in Human Prostate Epithelial Cells |
title_full | Cadmium Induces p53-Dependent Apoptosis in Human Prostate Epithelial Cells |
title_fullStr | Cadmium Induces p53-Dependent Apoptosis in Human Prostate Epithelial Cells |
title_full_unstemmed | Cadmium Induces p53-Dependent Apoptosis in Human Prostate Epithelial Cells |
title_short | Cadmium Induces p53-Dependent Apoptosis in Human Prostate Epithelial Cells |
title_sort | cadmium induces p53-dependent apoptosis in human prostate epithelial cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3308998/ https://www.ncbi.nlm.nih.gov/pubmed/22448262 http://dx.doi.org/10.1371/journal.pone.0033647 |
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