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Antiangiogenic activity of berberine is mediated through the downregulation of hypoxia-inducible factor-1, VEGF, and proinflammatory mediators.
MedLine Citation:
PMID:  22145808     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Berberine, a naturally occurring isoquinoline alkaloid, is present in a number of important medicinal plants. Berberine has a wide range of biochemical and pharmacological effects, including anticancer effects. In this study, we elucidated the mechanism of antiangiogenic activity of berberine using in vivo and in vitro models. In vivo antiangiogenic activity was studied using B16F-10 melanoma cells and induced capillary formation in C57BL/6 mice. Berberine, at 10 mg/kg body weight, showed significant inhibition in tumor-directed capillary formation and in various proangiogenic factors, such as vascular endothelial growth factor (VEGF), and proinflammatory mediators, such as interleukin (IL)-1β, IL-6, tumor necrosis factor alpha (TNF-α), and granulocyte macrophage colony-stimulating factor (GM-CSF), which are involved in tumor angiogenesis. At the same time, it could also increase antitumor factors, such as IL-2 and tissue-inhibitor metalloproteinase (TIMP) levels in the serum. Berberine could also inhibit endothelial motility, migration, tube formation, and vessel sprouting from rat aortic ring in vitro. Further, berberine inhibited various transcription factors involved in tumor development and angiogenesis, such as NF-ĸB, c-Fos, CREB, and ATF-2. mRNA expression levels of proangiogenic factors, such as cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and hypoxia-inducible factor (HIF), were also downregulated in tumor cells after treatment with berberine. Drastically elevated expressions of HIF and VEGF mRNA by tumor cells under hypoxic conditions were also decreased after treatment with berberine. This result clearly demonstrates that the antiangiogenic activity of berberine is mainly mediated through the inhibition of various proinflammatory and pro-angiogenic factors and the major ones are HIF, VEGF, COX-2, NO, NF-ĸB, and proinflammatory cytokines.
Authors:
T P Hamsa; Girija Kuttan
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Drug and chemical toxicology     Volume:  35     ISSN:  1525-6014     ISO Abbreviation:  Drug Chem Toxicol     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2011-12-07     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7801723     Medline TA:  Drug Chem Toxicol     Country:  England    
Other Details:
Languages:  eng     Pagination:  57-70     Citation Subset:  IM    
Affiliation:
Amala Cancer Research Center , Amala Nagar, Thrissur , India.
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