| Concomitant reduction of matrix metalloproteinase-2 secretion and intracellular reactive oxygen species following anti-sense inhibition of telomerase activity in PC-3 prostate carcinoma cells. | |
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MedLine Citation:
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PMID: 16013445 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: The level of activity of the telomerase has been shown to correlate with the degree of invasiveness in several tumor types. In addition, cellular redox state is believed to regulate the secretion of matrix metalloproteinase-2 (MMP-2). AIMS: To determine the effect of anti-sense telomerase treatment of prostate cancer cells on MMP-2 activity, and the reactive oxygen and nitrogen species (two effectors of cellular redox state). METHODS: Anti-sense oligonucleotide against RNA component of human telomerase (hTR) was introduced into the cells using Fugene-6 transfection reagent. The activity of telomerase was assessed using Telomere Repeat Amplification Protocol (TRAP assay). Activity of matrix metalloproteinase-2 (MMP-2) was determined by zymography. Levels of intracellular reactive oxygen species (ROS) and nitric oxide metabolites were measured by dichlorofluorescein diacetate (DCFH-DA) staining and Griess reagent, respectively. The level of apoptosis was determined using TUNEL assay. RESULTS: TRAP assay showed more than 90% inhibition of telomerase activity after 72 h of transfection. Pro-MMP-2 activity was decreased down to 50% of the control levels. Intracellular reactive oxygen species were also significantly decreased. Neither apoptosis rate nor the level of nitric oxide metabolites was significantly different between anti-sense treated and control cells. CONCLUSIONS: Concomitant reduction of the pro-MMP-2 secretion and ROS in PC-3 cells following hTR inhibition suggests that over-activity of telomerase in cancer cells might increase the level of matrix metalloproteinase-2 and thus, be directly involved in the invasion process through enhancement of intracellular oxidative stress. |
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Authors:
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Ahmad Shariftabrizi; Mohammad Reza Khorramizadeh; Farshid Saadat; Kamran Alimoghadam; Farnaz Safavifar; Mohammad Reza Ebrahimkhani |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Molecular and cellular biochemistry Volume: 273 ISSN: 0300-8177 ISO Abbreviation: Mol. Cell. Biochem. Publication Date: 2005 May |
Date Detail:
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Created Date: 2005-07-14 Completed Date: 2005-09-13 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0364456 Medline TA: Mol Cell Biochem Country: Netherlands |
Other Details:
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Languages: eng Pagination: 109-16 Citation Subset: IM |
Affiliation:
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Hematology, Oncology and BMTResearch Center, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis DNA-Binding Proteins / antagonists & inhibitors*, genetics, metabolism Humans Male Matrix Metalloproteinase 2 / antagonists & inhibitors, secretion* Oligonucleotides, Antisense / pharmacology* Oxidation-Reduction Oxidative Stress Prostatic Neoplasms / enzymology* Reactive Oxygen Species / metabolism* Telomerase / antagonists & inhibitors*, genetics, metabolism Tumor Cells, Cultured |
| Chemical | |
Reg. No./Substance:
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0/DNA-Binding Proteins; 0/Oligonucleotides, Antisense; 0/Reactive Oxygen Species; EC 2.7.7.49/Telomerase; EC 3.4.24.24/Matrix Metalloproteinase 2 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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