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Biochemistry (Moscow)

, Volume 73, Issue 2, pp 209–218 | Cite as

Inhibition of tumor specific angiogenesis by amentoflavone

  • C. Guruvayoorappan
  • G. KuttanEmail author
Article

Abstract

The formation of new capillaries from existing blood vessels is critical for tumor growth and metastasis. In this study we report that amentoflavone, a biflavonoid from Biophytum sensitivum, could inhibit the process of angiogenesis. Amentoflavone at nontoxic concentrations (0.05–0.2 μg/ml) showed significant inhibition in the proliferation, migration, and tube formation of endothelial cells, which are key events in the process of angiogenesis. In vivo studies in C57BL/6 mice using amentoflavone showed remarkable inhibition (52.9%) of tumor directed capillary formation. Amentoflavone showed inhibitory effect on the production of various endogenous factors such as IL-1β, IL-6, TNF-α, GM-CSF, and VEGF that control the process of angiogenesis. Amentoflavone treatment could increase the production of IL-2 and TIMP-1, which could successfully shift the equilibrium towards an angiostatic condition. The antiangiogenic activity of amentoflavone was supported by its remarkable suppression in sprouting of microvessels from rat aorta. Our results also show that amentoflavone could inhibit the production of VEGF mRNA in B16–F10 cells. These findings indicate that amentoflavone inhibits angiogenesis by disrupting the integrity of endothelial cells and by altering the endogenous factors that are required for the process of neovascularization.

Key words

amentoflavone angiogenesis endothelial cells proinflammatory cytokines tube formation 

Abbreviations

bFGF

basic fibroblast growth factor

ELISA

enzyme-linked immunosorbent assay

FCS

fetal calf serum

GM-CSF

granulocyte monocyte colony stimulating factor

HUVEC

human umbilical vein endothelial cell

IL

interleukin

iNOS

inducible nitric oxide synthase

MMP

matrix metalloproteinase

MTT

3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

TIMP

tissue inhibitor of metalloproteinase

TNF

tumor necrosis factor

VEGF

vascular endothelial growth factor

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Copyright information

© Pleiades Publishing, Ltd. 2008

Authors and Affiliations

  1. 1.Department of ImmunologyAmala Cancer Research Centre, Amala NagarThrissurIndia

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