| Nox1 downstream of 12-lipoxygenase controls cell proliferation but not cell spreading of colon cancer cells. | |
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MedLine Citation:
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PMID: 18076063 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The catalytic subunit of the NADPH oxidase complex, Nox1 (homologue of gp91phox/Nox2), expressed mainly in intestinal epithelial and vascular smooth muscle cells, functions in innate immune defense and cell proliferation. The molecular mechanisms underlying these functions, however, are not completely understood. We measured Nox1-dependent O2- production during cell spreading on Collagen IV (Coll IV) in colon carcinoma cell lines. Knocking down Nox1 by shRNA, we showed that Nox1-dependent O2- production is activated during cell spreading after 4 hr of adhesion on Collagen IV. Nox1 activation during cell spreading relies on Rac1 activation and arachidonic metabolism. Our results showed that manoalide (a secreted phospholipase A2 inhibitor) and cinnamyl-3,4-dihydroxy-alpha-cyanocinnamate (a 12-lipoxygenase inhibitor) inhibit O2- production, cell spreading and cell proliferation in these colonic epithelial cells. 12-Lipoxygenase inhibition of ROS production and cell spreading can be reversed by adding 12-HETE, a 12-lipoxygenase product, supporting the specific effect observed with cinnamyl-3,4-dihydroxy-alpha-cyanocinnamate. In contrast, Nox1 shRNA and DPI (NADPH oxidase inhibitor) weakly affect cell spreading while inhibiting O2- production and cell proliferation. These results suggest that the 12-lipoxygenase pathway is upstream of Nox1 activation and controls cell spreading and proliferation, while Nox1 specifically affects cell proliferation. |
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Authors:
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Daniela D de Carvalho; Amine Sadok; Véronique Bourgarel-Rey; Florence Gattacceca; Claude Penel; Maxime Lehmann; Hervé Kovacic |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: International journal of cancer. Journal international du cancer Volume: 122 ISSN: 1097-0215 ISO Abbreviation: Int. J. Cancer Publication Date: 2008 Apr |
Date Detail:
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Created Date: 2008-02-25 Completed Date: 2008-03-06 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0042124 Medline TA: Int J Cancer Country: United States |
Other Details:
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Languages: eng Pagination: 1757-64 Citation Subset: IM |
Affiliation:
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CNRS FRE 2737, Cytosquelette et Intégration des Signaux du Microenvironnement Tumoral (CISMET), Aix-Marseille Université, France. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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12-Hydroxy-5,8,10,14-eicosatetraenoic Acid
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pharmacology Arachidonate 12-Lipoxygenase / antagonists & inhibitors, metabolism* Blotting, Western Caffeic Acids / pharmacology Carcinoma / enzymology, metabolism*, pathology* Cell Line, Tumor Cell Proliferation Colonic Neoplasms / enzymology, metabolism*, pathology* Enzyme Activation Humans NADPH Oxidase / metabolism* Phosphodiesterase Inhibitors / pharmacology Phospholipases A2 / antagonists & inhibitors RNA / isolation & purification Reactive Oxygen Species / metabolism* Reverse Transcriptase Polymerase Chain Reaction Terpenes / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Caffeic Acids; 0/Phosphodiesterase Inhibitors; 0/Reactive Oxygen Species; 0/Terpenes; 0/cinnamyl-3,4-dihydroxycyanocinnamate; 59985-28-3/12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; 63231-63-0/RNA; 75088-80-1/manoalide; EC 1.13.11.31/Arachidonate 12-Lipoxygenase; EC 1.6.3.-/NOX1 protein, human; EC 1.6.3.1/NADPH Oxidase; EC 3.1.1.4/Phospholipases A2 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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