Vernolide-A inhibits radiation-induced hypoxia-mediated tumor angiogenesis by regulating HIF-1α, MMP-2, MMP-9, and VEGF

Amala Cancer Research Centre, Amala Nagar, Thrissur-680555, Kerala State, India.
Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer 01/2011; 30(2):139-51. DOI: 10.1615/JEnvironPatholToxicolOncol.v30.i2.50
Source: PubMed


We investigated the effect of vernolide-A on the inhibition of radiation-induced tumor angiogenesis in C57BL/6 mice. Vernolide-A administration significantly reduced the tumor volume of radiation-exposed mice. Serum vascular endothelial growth factor (VEGF) levels were drastically elevated during tumor progression and irradiation and were significantly reduced by treatment with vernolide-A. Immunohistochemical analysis also revealed reduced vascular density after treatment with vernolide-A, and 3H-thymidine incorporation assay and soft agar assay showed that vernolide-A could inhibit the proliferation of B16F-10 melanoma cells in vitro along with radiation. Vernolide-A also caused a significant inhibition in the invasion of irradiated B16F-10 melanoma cells across the collagen matrix, and inhibited the radiation-induced gene expression of hypoxia-inducible transcription factor-1α (HIF-1α) and VEGF in B16F-10 cells and VEGF receptor (Flk-1) expression in human umbilical vein endothelial cells. Gelatin zymographic analysis showed that vernolide-A could also inhibit the radiation-induced activation of matrix metalloproteinases (MMPs). Our results indicate that vernolide-A inhibits radiation-induced tumor angiogenesis by regulating HIF-1α, MMP-2, MMP-9, and VEGF.

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Available from: Poyil Pratheeshkumar
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    • "Much attention has been given to the Phase I/II trial of carboplatin, taxol and sorafenib (Nexavar, Bayer Pharmaceuticals Corporation, West Haven, CT and Onyx Pharmaceuticals, Emeryville, CA), a multi-tyrosine kinase inhibitor with activity against both the MAP kinase and VEGF-R2-signalling pathways (Mehnert et al, 2010). Additional ongoing trials of novel agents that target VEGF and its receptors include also the study of Vernolide-A (Pratheeshkumar and Kuttan, 2011) that in B16F-10 melanoma cells inhibit tumour angiogenesis by regulating HIF-1a, MMP-2, MMP-9 and VEGF. "
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