TITLE

Cadmium Induces p53-Dependent Apoptosis in Human Prostate Epithelial Cells

AUTHOR(S)
Aimola, Pierpaolo; Carmignani, Marco; Volpe, Anna Rita; Di Benedetto, Altomare; Claudio, Luigi; Waalkes, Michael P.; Van Bokhoven, Adrie; Tokar, Erik J.; Claudio, Pier Paolo
PUB. DATE
March 2012
SOURCE
PLoS ONE;Mar2012, Vol. 7 Issue 3, p1
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
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 CdCl2 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 CdCl2 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.
ACCESSION #
77585709

 

Related Articles

  • 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;Mar2012, Vol. 7 Issue 3, p1 

    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...

  • Autoproteolysis of PIDD marks the bifurcation between pro-death caspase-2 and pro-survival NF-κB pathway. Tinel, Antoine; Janssens, Sophie; Lippens, Saskia; Cuenin, Solange; Logette, Emmanuelle; Jaccard, Bastienne; Quadroni, Manfredo; Tschopp, Jürg // EMBO Journal;1/10/2007, Vol. 26 Issue 1, p197 

    Upon DNA damage, a complex called the PIDDosome is formed and either signals NF-κB activation and thus cell survival or alternatively triggers caspase-2 activation and apoptosis. PIDD (p53-induced protein with a death domain) is constitutively processed giving rise to a 48-kDa N-terminal...

  • p53-Induced Apoptosis and Inhibitors of p53. Nayak, Surendra Kumar; Panesar, Paramjit Singh; Kumar, Harish // Current Medicinal Chemistry;Jul2009, Vol. 16 Issue 21, p2627 

    Protein p53 is a key player in mitochondrial mediated apoptotic cell death and excess p53 activity has been implicated in many disease states such athrosclerosis, diabetes, osteoarthritis, Alzheimer's disease, Parkinson's disease, Huntington's disease, AIDS, P. falciparum and S. typhimurium...

  • Interrelation of Cell Apoptosis and Proliferation in the Thymus during Its Involution. Linkova, N.; Polyakova, V.; Kvetnoy, I. // Bulletin of Experimental Biology & Medicine;Aug2011, Vol. 151 Issue 4, p460 

    In people over 60 years, thymocytes contain proliferation protein Ki67 and proapoptotic protein P53. During aging, apoptosis of thymus cell prevails over proliferation, though thymocytes retain proliferative capacity even in long-livers.

  • Inactivation of HAUSP in vivo modulates p53 function. Kon, N.; Kobayashi, Y.; Li, M.; Brooks, C. L.; Ludwig, T.; Gu, W. // Oncogene;3/4/2010, Vol. 29 Issue 9, p1270 

    Hausp is a deubiquitinase that has been shown to regulate the p53–Mdm2 pathway. Cotransfection of p53 and Hausp stabilizes p53 through the removal of ubiquitin moieties from polyubiquitinated p53. Interestingly, knockout or RNA interference-mediated knockdown of Hausp in human cells also...

  • P63 regulates tubular formation via epithelial-to-mesenchymal transition. Zhang, Y; Yan, W; Chen, X // Oncogene;3/20/2014, Vol. 33 Issue 12, p1548 

    P63, a p53 family member, is expressed as TA and ΔN isoforms. Interestingly, both TAp63 and ΔNp63 are transcription factors, and regulate both common and distinct sets of target genes. p63 is required for survival of some epithelial cell lineages, and lack of p63 leads to loss of...

  • Silver nanoparticles induce p53-mediated apoptosis in human bronchial epithelial (BEAS-2B) cells. Ha Ryong Kim; Da Young Shin; Yong Joo Park; Chang We Park; Seung Min Oh; Kyu Hyuck Chung // Journal of Toxicological Sciences;Jun2014, Vol. 39 Issue 3, p401 

    Deregulated apoptosis has been associated with many lung diseases. Although many studies have reported the apoptotic effects exhibited by silver nanoparticles (Ag-NPs) in various circumstances, the apoptosis mechanism of Ag-NPs is unclear. We investigated oxidative stress and apoptosis in human...

  • P53 protein in proliferation, repair and apoptosis of cells. Wawryk-Gawda, Ewelina; Chylińska-Wrzos, Patrycja; Lis-Sochocka, Marta; Chłapek, Katarzyna; Bulak, Kamila; Jędrych, Marian; Jodłowska-Jędrych, Barbara // Protoplasma;May2014, Vol. 251 Issue 3, p525 

    The p53 protein is an important factor of many intra- and extracellular processes. This protein regulates the repair of cellular DNA and induces apoptosis. It is also responsible for the regulation of the senescence and the cell entering the subsequent stages of the cellular cycle. The protein...

  • Modulation of p53 transcriptional activity by PRIMA-1 and Pifithrin-α on staurosporine-induced apoptosis of wild-type and mutated p53 epithelial cells. Charlot, J. F.; Nicolier, M.; Prétet, J. L.; Mougin, C. // Apoptosis;Sep2006, Vol. 11 Issue 5, p813 

    We recently argued for a major role of p53 in staurosporine(ST)-induced apoptosis of immortalized epithelial cells, depending on their p53 status. Here, we studied the effects of PRIMA-1 ( p53 reactivation and induction of massive apoptosis) and Pifithrin-α ( p fifty- three inhibitor) in...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics