| 13 cis-retinoic acid regulates cytokine production and inhibits angiogenesis by disrupting endothelial cell migration and tube formation. | |
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MedLine Citation:
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PMID: 19066126 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cancer prevention using natural products has become an integral part of cancer control. In this study we investigated the effect of 13-cis-retinoic acid on the inhibition of angiogenesis using in vivo as well as in vitro models. Our studies using animal model reveled that 13-cis-retinoic acid could significantly (p < 0.001) inhibit the tumor directed capillaries. The cytokine profile in the serum of these animals showed a drastically increased level of proinflammatory cytokines such as IL-1beta, TNF-alpha, IL-6, GM-CSF and the direct endothelial cell proliferating agent, VEGF during the onset of angiogenesis. Administration of 13-cis-retinoic acid could differentially regulate these cytokine's elevation. The differential elevation is further evidenced by the increased production of IL-2 and tissue inhibitor of metalloprotease-1 (TIMP-1) in the 13-cis-retinoic acid treated animals. Aortic ring assay for in vitro angiogenesis revealed that 13-cis-retinoic acid could markedly inhibit the microvessel sprouting. Moreover, 13-cis-retinoic acid was able to inhibit vascular endothelial cell proliferation, migration and tube formation. Furthermore, 13-cis-retinoic acid treatment could inhibit the activation and nuclear translocation of p65, p50, c-Rel subunits of nuclear factor-KB, and other transcription factors such as c-fos, activated transcription factor-2, and cyclic adenosine monophosphate response element-binding protein in B16F-10 melanoma cells. These findings suggest that the anti-angiogenic potential of 13-cis-retinoic acid is mediated through inhibition of endothelial cell migration and tube formation and altered cytokine production during the onset of angiogenesis. |
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Authors:
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Chandrasekharan Guruvayoorappan; Girija Kuttan |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Journal of experimental therapeutics & oncology Volume: 7 ISSN: 1359-4117 ISO Abbreviation: J. Exp. Ther. Oncol. Publication Date: 2008 |
Date Detail:
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Created Date: 2008-12-10 Completed Date: 2009-01-15 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9604933 Medline TA: J Exp Ther Oncol Country: United States |
Other Details:
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Languages: eng Pagination: 173-82 Citation Subset: IM |
Affiliation:
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Department of Immunology, Amala Cancer Research Centre, Amala Nagar, Thrissur 680 555, Kerala State, India. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Angiogenesis Inhibitors
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therapeutic use* Animals Cell Movement / drug effects* Cell Nucleus / metabolism Cell Proliferation / drug effects Cytokines / biosynthesis* Endothelium, Vascular / drug effects*, metabolism Gene Expression Regulation, Neoplastic / drug effects Humans Isotretinoin / therapeutic use* Male Mice Mice, Inbred C57BL NF-kappa B / metabolism Neovascularization, Pathologic / prevention & control* Rats Rats, Sprague-Dawley Transcription Factors / metabolism Umbilical Veins / cytology, drug effects, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Angiogenesis Inhibitors; 0/Cytokines; 0/NF-kappa B; 0/Transcription Factors; 4759-48-2/Isotretinoin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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