Document Detail


13 cis-retinoic acid regulates cytokine production and inhibits angiogenesis by disrupting endothelial cell migration and tube formation.
MedLine Citation:
PMID:  19066126     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Chandrasekharan Guruvayoorappan; Girija Kuttan
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of experimental therapeutics & oncology     Volume:  7     ISSN:  1359-4117     ISO Abbreviation:  J. Exp. Ther. Oncol.     Publication Date:  2008  
Date Detail:
Created Date:  2008-12-10     Completed Date:  2009-01-15     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9604933     Medline TA:  J Exp Ther Oncol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  173-82     Citation Subset:  IM    
Affiliation:
Department of Immunology, Amala Cancer Research Centre, Amala Nagar, Thrissur 680 555, Kerala State, India.
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MeSH Terms
Descriptor/Qualifier:
Angiogenesis Inhibitors / 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:
0/Angiogenesis Inhibitors; 0/Cytokines; 0/NF-kappa B; 0/Transcription Factors; 4759-48-2/Isotretinoin

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