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Metallomics Vol - 5 Issue - 4

Metallomics Vol - 5 Issue - 3

Metallomics Vol - 5 Issue - 2

Comparative proteomics analysis of sodium selenite-induced apoptosis in human prostate cancer cells

Content Provider	Royal Society of Chemistry (RSC)
Author	Chen, Ping Wang, Lixiang Li, Na Liu, Qiong Ni, Jiazuan
Copyright Year	2013
Abstract	Selenium is an important trace mineral necessary for human health. Clinical trials have shown potential inhibitory effects of selenium in advanced or aggressive prostate cancer. However, its mechanism of action remains unclear. This study investigated the mechanism of action of sodium selenite in human prostate cancer PC-3 cells using proteomics. CCK-8 assays were used to detect cell viability and the inhibitory rate. Cell apoptosis was detected by annexin V-FITC and propidium iodide double staining using flow cytometry. Selenite inhibited the growth of PC-3 cells causing them to display morphological changes typical of apoptosis. The rate of cell apoptosis also increased. Proteomics identified a variety of differentially expressed proteins in PC-3 cells exposed to selenite. Eighteen protein spots were identified by MALDI-TOF mass spectrometry. These proteins were separated into those involved in redox balance, protein degradation and cellular energy metabolism. Three differently expressed proteins (SOD1, Stathmin and Erp29) were chosen for Western blot verification, together with several apoptosis-related proteins. Western blot analyses showed that selenite-induced apoptosis was accompanied by activation of caspase-8 and specific proteolytic cleavage of PARP. This led to an increase in the pro-apoptotic protein Bax, and to a decrease in the anti-apoptotic protein Bcl-2 and in hypoxia inducible factor-1α. Increased ROS generation and decreased mitochondrial membrane potential were consistent with reduced expression of antioxidative proteins identified by comparative proteomics. We therefore propose that sodium selenite induces the apoptosis of PC-3 cells mainly through the mitochondrial pathway, but also via ER stress and HIF-1α mediated pathways.
Starting Page	541
Ending Page	550
Page Count	10
File Format	HTM / HTML PDF
ISSN	17565901
Volume Number	5
Issue Number	5
Journal	Metallomics
DOI	10.1039/c3mt00002h
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	Western blot Bcl-2 Flow cytometry Reactive oxygen species Propidium iodide Superoxide dismutase Tumor hypoxia Mineral (nutrient) Selenium Membrane potential PC3 Sodium selenite Redox Caspase Metabolism Antioxidant Protein Bcl-2-associated X protein Ionization Proteomics Bax Prostate cancer Mass spectrometry Endoplasmic reticulum Annexin Apoptosis
Content Type	Text
Resource Type	Article
Subject	Chemistry Medicine Metals and Alloys Biochemistry Biomaterials Biophysics

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