Journal article
Apoptosis induced by selenomethionine and methioninase is superoxide-mediated and p53-dependent in human prostate cancer cells
Molecular cancer therapeutics, Vol.5(12), pp.3275-3284
12/2006
DOI: 10.1158/1535-7163.MCT-06-0400
PMCID: PMC1761114
PMID: 17172431
Abstract
Selenomethionine (SeMet) is the chemical form or major component of selenium used for cancer chemoprevention in several clinical trials. However, evidence from experimental studies indicates that SeMet has weaker anticancer effects than most other forms of selenium. Recent studies showed that the anticancer activity of SeMet can be enhanced by methioninase (METase), indicating that SeMet metabolites are responsible for its anticancer activity. In the present study, we demonstrated that wild-type p53-expressing LNCaP human prostate cancer cells were more sensitive to co-treatment with SeMet and METase than p53-null PC3 human prostate cancer cells. SeMet and METase co-treatment significantly increased levels of superoxide and apoptosis in LNCaP cells. Co-treatment with SeMet and METase resulted in increased levels of phosphorylated p53 (serine15), total p53, Bax, and p21
Waf1
proteins. LNCaP cells treated with SeMet and METase also showed p53 translocation to mitochondria, decreased mitochondrial membrane potential, cytochrome c release into the cytosol, and activation of caspase 9. The effects of SeMet and METase were suppressed by pre-treatment with a synthetic superoxide dismutase mimic or by knockdown of p53 via RNA interference. Reexpression of wild-type p53 in PC3 cells resulted in increases in superoxide production, apoptosis, and caspase 9 activity, and a decrease in mitochondrial membrane potential following co-treatment with SeMet and METase. Our study demonstrates that apoptosis induced by SeMet plus METase is superoxide-mediated and p53-dependent via mitochondrial pathway(s). These results suggest that superoxide and p53 may play a role in cancer chemoprevention by selenium.
Details
- Title: Subtitle
- Apoptosis induced by selenomethionine and methioninase is superoxide-mediated and p53-dependent in human prostate cancer cells
- Creators
- Rui Zhao - The Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792Frederick E Domann - Free Radical and Radiation Biology Program, University of Iowa, Iowa City, IA 52242Weixiong Zhong - The Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792
- Resource Type
- Journal article
- Publication Details
- Molecular cancer therapeutics, Vol.5(12), pp.3275-3284
- DOI
- 10.1158/1535-7163.MCT-06-0400
- PMID
- 17172431
- PMCID
- PMC1761114
- ISSN
- 1535-7163
- eISSN
- 1538-8514
- Language
- English
- Date published
- 12/2006
- Academic Unit
- Pathology; Surgery; Radiation Oncology
- Record Identifier
- 9984047720602771
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