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...

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Autores principales:	Pierpaolo Aimola, Marco Carmignani, Anna Rita Volpe, Altomare Di Benedetto, Luigi Claudio, Michael P Waalkes, Adrie van Bokhoven, Erik J Tokar, Pier Paolo Claudio
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fe0763f755e445ce842277e727d36a8a
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spelling	oai:doaj.org-article:fe0763f755e445ce842277e727d36a8a2021-11-18T07:24:40ZCadmium induces p53-dependent apoptosis in human prostate epithelial cells.1932-620310.1371/journal.pone.0033647https://doaj.org/article/fe0763f755e445ce842277e727d36a8a2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22448262/?tool=EBIhttps://doaj.org/toc/1932-6203Cadmium, 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.Pierpaolo AimolaMarco CarmignaniAnna Rita VolpeAltomare Di BenedettoLuigi ClaudioMichael P WaalkesAdrie van BokhovenErik J TokarPier Paolo ClaudioPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 3, p e33647 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Pierpaolo Aimola Marco Carmignani Anna Rita Volpe Altomare Di Benedetto Luigi Claudio Michael P Waalkes Adrie van Bokhoven Erik J Tokar Pier Paolo Claudio Cadmium induces p53-dependent apoptosis in human prostate epithelial cells.
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	article
author	Pierpaolo Aimola Marco Carmignani Anna Rita Volpe Altomare Di Benedetto Luigi Claudio Michael P Waalkes Adrie van Bokhoven Erik J Tokar Pier Paolo Claudio
author_facet	Pierpaolo Aimola Marco Carmignani Anna Rita Volpe Altomare Di Benedetto Luigi Claudio Michael P Waalkes Adrie van Bokhoven Erik J Tokar Pier Paolo Claudio
author_sort	Pierpaolo Aimola
title	Cadmium induces p53-dependent apoptosis in human prostate epithelial cells.
title_short	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_sort	cadmium induces p53-dependent apoptosis in human prostate epithelial cells.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/fe0763f755e445ce842277e727d36a8a
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_version_	1718423512530550784

Cadmium induces p53-dependent apoptosis in human prostate epithelial cells.

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