Document Detail


NOX5 NAD(P)H oxidase regulates growth and apoptosis in DU 145 prostate cancer cells.
MedLine Citation:
PMID:  12686516     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Reactive oxygen species (ROS) appear to play an important role in regulating growth and survival of prostate cancer. However, the sources for ROS production in prostate cancer cells have not been determined. We report that ROS are generated by intact American Type Culture Collection DU 145 cells and by their membranes through a mechanism blocked by NAD(P)H oxidase inhibitors. ROS are critical for growth in these cells, because NAD(P)H oxidase inhibitors and antioxidants blocked proliferation. Components of the human phagocyte NAD(P)H oxidase, p22phox and gp91phox, as well as the Ca2+ concentration-responsive gp91phox homolog NOX5 were demonstrated in DU 145 cells by RT-PCR and sequencing. Although the protein product for p22phox was not detectable, both gp91phox and NOX5 were identified throughout the cell by immunostaining and confocal microscopy and NOX5 immunostaining was enhanced in a perinuclear location, corresponding to enhanced ROS production adjacent to the nuclear membrane imaged by 2',7'-dichlorofluorescin diacetate oxidation. The calcium ionophore ionomycin dramatically stimulated ferricytochrome c reduction in cell media, further supporting the importance of NOX5 for ROS production. Antisense oligonucleotides for NOX5 inhibited ROS production and cell proliferation in DU 145 cells. In contrast, antisense oligonucleotides to p22phox or gp91phox did not impair cell growth. Inhibition of ROS generation with antioxidants or NAD(P)H oxidase inhibitors increased apoptosis in cells. These results indicate that ROS generated by the newly described NOX5 oxidase are essential for prostate cancer growth, possibly by providing trophic intracellular oxidant tone that retards programmed cell death.
Authors:
Sukhdev S Brar; Zachary Corbin; Thomas P Kennedy; Richelle Hemendinger; Lisa Thornton; Bettina Bommarius; Rebecca S Arnold; A Richard Whorton; Anne B Sturrock; Thomas P Huecksteadt; Mark T Quinn; Kevin Krenitsky; Kristia G Ardie; J David Lambeth; John R Hoidal
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.     Date:  2003-04-09
Journal Detail:
Title:  American journal of physiology. Cell physiology     Volume:  285     ISSN:  0363-6143     ISO Abbreviation:  Am. J. Physiol., Cell Physiol.     Publication Date:  2003 Aug 
Date Detail:
Created Date:  2003-07-04     Completed Date:  2003-09-05     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  100901225     Medline TA:  Am J Physiol Cell Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  C353-69     Citation Subset:  IM    
Affiliation:
Department of Internal Medicine, Carolinas Medical Center, Charlotte, NC 28232, USA.
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MeSH Terms
Descriptor/Qualifier:
Antioxidants / pharmacology
Apoptosis / drug effects,  genetics*
Carcinoma / enzymology*
Cell Division / drug effects,  genetics*
Cell Transformation, Neoplastic / drug effects,  metabolism
Cytochrome c Group / drug effects,  metabolism
Enzyme Inhibitors / pharmacology
Humans
Ionophores / pharmacology
Male
Membrane Glycoproteins / metabolism
Membrane Proteins / antagonists & inhibitors,  genetics,  metabolism*
NADPH Oxidase / antagonists & inhibitors,  genetics,  metabolism*
Nuclear Envelope / metabolism
Oligoribonucleotides, Antisense / pharmacology
Oxidative Stress / drug effects,  physiology
Prostatic Neoplasms / enzymology*
RNA, Messenger / drug effects,  metabolism
Reactive Oxygen Species / metabolism*
Tumor Cells, Cultured
Grant Support
ID/Acronym/Agency:
CA-84138/CA/NCI NIH HHS; HL-42426/HL/NHLBI NIH HHS; HL-50153-07/HL/NHLBI NIH HHS; HL-61377/HL/NHLBI NIH HHS; HL-66575/HL/NHLBI NIH HHS; HL-67281/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Antioxidants; 0/CYBB protein, human; 0/Cytochrome c Group; 0/Enzyme Inhibitors; 0/Ionophores; 0/Membrane Glycoproteins; 0/Membrane Proteins; 0/Oligoribonucleotides, Antisense; 0/RNA, Messenger; 0/Reactive Oxygen Species; EC 1.6.-/NOX5 protein, human; EC 1.6.3.1/NADPH Oxidase

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