Journal article
Expression of p53 Enhances Selenite-Induced Superoxide Production and Apoptosis in Human Prostate Cancer Cells
Cancer research (Chicago, Ill.), Vol.66(4), pp.2296-2304
02/15/2006
DOI: 10.1158/0008-5472.CAN-05-2216
PMCID: PMC1435866
PMID: 16489034
Abstract
Although the anticancer effects of selenium have been demonstrated in clinical, preclinical, and laboratory studies, the underlying mechanism(s) remain unclear. Our previous study demonstrated that sodium selenite induced LNCaP human prostate cancer cell apoptosis in association with production of reactive oxygen species, alteration of cell redox state, and mitochondrial damage. In the present study, we demonstrated that selenite-induced apoptosis was superoxide-mediated and p53-dependent via mitochondrial pathways. In addition, we also demonstrated that superoxide production by selenite was p53-dependent. Our study showed that wild-type p53 expressing LNCaP cells were more sensitive to selenite-induced apoptosis than p53-null PC3 cells. Selenite treatment resulted in high levels of superoxide production in LNCaP cells, but only low levels in PC3 cells. LNCaP cells also showed sequential increases in levels of phosphorylated p53 (Serine15), total p53, Bax, and p21
Waf1
proteins following selenite treatment. The effects of selenite were suppressed by pre-treatment with a synthetic superoxide dismutase mimic or by knockdown of p53 via RNA interference. LNCaP cells treated with selenite also showed p53 translocation to mitochondria, cytochrome c release into the cytosol, and activation of caspase 9. On the other hand, restoration of wild-type p53 expression in PC3 cells increased cellular sensitivity to selenite and resulted in increased superoxide production, caspase 9 activation, and apoptosis following selenite treatment. These results suggest that selenite induces apoptosis by producing superoxide to activate p53 and to induce p53 mitochondrial translocation. Activation of p53 in turn synergistically enhances superoxide production and apoptosis induced by selenite.
Details
- Title: Subtitle
- Expression of p53 Enhances Selenite-Induced Superoxide Production and Apoptosis in Human Prostate Cancer Cells
- Creators
- Rui Zhao - The Department of Pathology and Laboratory Medicine, University of Wisconsin Medical School, Madison, WI 53792Nong Xiang - The Department of Pathology and Laboratory Medicine, University of Wisconsin Medical School, Madison, WI 53792Frederick E Domann - Free Radical and Radiation Biology Program, University of Iowa, Iowa City, IA 52242 andWeixiong Zhong - The Department of Pathology and Laboratory Medicine, University of Wisconsin Medical School, Madison, WI 53792
- Resource Type
- Journal article
- Publication Details
- Cancer research (Chicago, Ill.), Vol.66(4), pp.2296-2304
- DOI
- 10.1158/0008-5472.CAN-05-2216
- PMID
- 16489034
- PMCID
- PMC1435866
- ISSN
- 0008-5472
- eISSN
- 1538-7445
- Language
- English
- Date published
- 02/15/2006
- Academic Unit
- Pathology; Surgery; Radiation Oncology
- Record Identifier
- 9984047652102771
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