| TARGETING HEPATOMA USING NO DONOR STRATEGIES. | |
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MedLine Citation:
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PMID: 22861189 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Aims: The study evaluated the role of increased intracellular nitric oxide (NO) concentration using NO donors or stably nitric oxide synthase-3 (NOS-3) overexpression during CD95-dependent cell death in hepatoma cells. The expression of cell death receptors and caspase activation, RhoA kinase activity, NOS-3 expression/activity, oxidative/nitrosative stress and p53 expression were analyzed. The antitumoral activity of NO was also evaluated in the subcutaneous implantation of NOS-3-overexpressing hepatoma cells, as well NO donor injection into wild type hepatoma-derived tumors implanted in xenograft mouse models. Results: NO donor increased CD95 expression, caspase-8 and -3 activation in HepG2, Huh7 and Hep3B cells. NOS-3 overexpression increased oxidative/nitrosative stress, p53 and CD95 expression, cellular Fas-associated death domain (FADD)-like IL-1beta converting enzyme (FLICE) inhibitory protein long (cFLIPL) and its short isoform (cFLIPS) shift, and cell death in HepG2 (4TO-NOS) cells. The inhibition of RhoA kinase and p53 knock-down using RNA interference reduced cell death in 4TO-NOS cells. The supplementation with H2O2 increased NOS-3 activity and cell death in 4TO-NOS cells. NOS-3 overexpression or NO donor injection into hepatoma-derived tumors reduced the size, increased p53 and cell death receptor expression in nude mice. Innovation and Conclusions: The increase of intracellular NO concentration promoted oxidative and nitrosative stress, Rho kinase activity, p53 and CD95 expression, and cell death in cultured hepatoma cells. NOS-3 overexpressed HepG2 cells or intratumoral NO donor administration reduced tumor cell growth and increased the expression of p53 and cell death receptors in tumors developed in xenograft mouse model. |
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Authors:
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Raul González; Gustavo Ferrín; Patricia Aguilar-Melero; Isidora Ranchal; Clara I Linares; Rosario I Bello; Manuel De la Mata; Vladimir Gogvadze; José Antonio Bárcena; José M Alamo; Sten Orrenius; Javier Padillo; Boris Zhivotovsky; Jordi Muntané |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-8-4 |
Journal Detail:
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Title: Antioxidants & redox signaling Volume: - ISSN: 1557-7716 ISO Abbreviation: Antioxid. Redox Signal. Publication Date: 2012 Aug |
Date Detail:
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Created Date: 2012-8-6 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100888899 Medline TA: Antioxid Redox Signal Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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University of Córdoba, Department of Biochemistry and Molecular Biology, Córdoba, Spain; raulangello@hotmail.com. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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