| Reactive oxygen species regulate properties of transformation in UROtsa cells exposed to monomethylarsonous acid by modulating MAPK signaling. | |
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MedLine Citation:
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PMID: 19014992 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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UROtsa cells exposed to 50 nM monomethylarsonous acid [MMA(III)] for 52 wk (MSC52) achieved hyperproliferation, anchorage independent growth, and enhanced tumorgenicity. MMA(III) has been shown to induce reactive oxygen species (ROS), which can lead to activation of signaling cascades causing stress-related proliferation of cells and even cellular transformation. Previous research established the acute activation of MAPK signaling cascade by ROS produced by MMA(III) as well as chronic up regulation of COX-2 and EGFR in MSC52 cells. To determine if ROS played a role in the chronic pathway perturbations by acting as secondary messengers, activation of Ras was determined in UROtsa cells [exposed to MMA(III) for 0-52 wk] and found to be increased through 52 wk most dramatically after 20 wk of exposure. Ras has been shown to cause an increase in O2(-) and be activated by increases in O2(-), making ROS important to study in the transformation process. COX-2 upregulation in MSC52 cells was confirmed by real time RT-PCR. By utilizing both antioxidants or specific COX inhibitors, it was shown that COX-2 upregulation was dependent on ROS, specifically, O2(-). In addition, because previous research established the importance of MAPK activation in phenotypic changes associated with transformation in MSC52 cells, it was hypothesized that ROS play a role in maintaining phenotypic characteristics of the malignant transformation of MSC52 cells. Several studies have demonstrated that cancer cells have lowered superoxide dismutase (MnSOD) activity and protein levels. Increasing levels of MnSOD have been shown to suppress the malignant phenotype of cells. SOD was added to MSC52 cells resulting in slower proliferation rates (doubling time=42h vs. 31h). ROS scavengers of OH also slowed proliferation rates of MSC52 cells. To further substantiate the importance of ROS in these properties of transformation in MSC52 cells, anchorage independent growth was assessed after the addition of antioxidants, both enzymatic and non-enzymatic. Scavengers of OH, and O2(-) blocked the colony formation of MSC52 cells. These data support the role for the involvement of ROS in properties of transformation of UROtsa cells exposed to MMA(III). |
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Authors:
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K E Eblin; T J Jensen; S M Wnek; S E Buffington; B W Futscher; A J Gandolfi |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2008-10-22 |
Journal Detail:
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Title: Toxicology Volume: 255 ISSN: 0300-483X ISO Abbreviation: Toxicology Publication Date: 2009 Jan |
Date Detail:
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Created Date: 2008-12-16 Completed Date: 2009-03-27 Revised Date: 2011-05-05 |
Medline Journal Info:
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Nlm Unique ID: 0361055 Medline TA: Toxicology Country: Ireland |
Other Details:
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Languages: eng Pagination: 107-14 Citation Subset: IM |
Affiliation:
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Department of Pharmacology and Toxicology, University of Arizona, USA. kyleeeblin@yahoo.com |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adenosine Triphosphate
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metabolism Antioxidants / pharmacology Blotting, Western Caspase 3 / metabolism Cell Line Cell Proliferation / drug effects Cell Transformation, Neoplastic / drug effects* Cyclooxygenase 2 / metabolism Genes, ras Humans Mitogen-Activated Protein Kinases / physiology* Nucleic Acids / metabolism Organometallic Compounds / toxicity* Oxygen Consumption / drug effects Reactive Oxygen Species / metabolism* Reverse Transcriptase Polymerase Chain Reaction Signal Transduction / physiology* |
| Grant Support | |
ID/Acronym/Agency:
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ES04940/ES/NIEHS NIH HHS; ES06694/ES/NIEHS NIH HHS; ES07091/ES/NIEHS NIH HHS; P42 ES004940-160021/ES/NIEHS NIH HHS; R01 CA127989-03/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antioxidants; 0/Nucleic Acids; 0/Organometallic Compounds; 0/Reactive Oxygen Species; 0/monomethylarsonous acid; 56-65-5/Adenosine Triphosphate; EC 1.14.99.1/Cyclooxygenase 2; EC 2.7.11.24/Mitogen-Activated Protein Kinases; EC 3.4.22.-/Caspase 3 |
| Comments/Corrections | |
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