Antiangiogenic activity of berberine is mediated through the downregulation of hypoxia-inducible factor-1, VEGF, and proinflammatory mediators
| Autor: | T. P. Hamsa, Girija Kuttan |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Male
Vascular Endothelial Growth Factor A Berberine Angiogenesis Health Toxicology and Mutagenesis Melanoma Experimental Down-Regulation Angiogenesis Inhibitors Pharmacology Toxicology Proinflammatory cytokine Rats Sprague-Dawley Mice chemistry.chemical_compound Downregulation and upregulation In vivo Cell Line Tumor Human Umbilical Vein Endothelial Cells Animals Humans RNA Messenger Mice Inbred BALB C Chemical Health and Safety Neovascularization Pathologic Public Health Environmental and Occupational Health Interleukin General Medicine Rats Gene Expression Regulation Neoplastic Mice Inbred C57BL Vascular endothelial growth factor chemistry Biochemistry Tumor necrosis factor alpha Hypoxia-Inducible Factor 1 Inflammation Mediators |
| Zdroj: | Drug and Chemical Toxicology. 35:57-70 |
| ISSN: | 1525-6014 0148-0545 |
| DOI: | 10.3109/01480545.2011.589437 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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