%0 Journal Article %A Pratheeshkumar, P. %A Kuttan, Girija %D 2011 %I Begell House %K radiotherapy; tumor hypoxia; angiogenesis; HIF-1a; MMPs; VEGF %N 2 %P 139-151 %R 10.1615/JEnvironPatholToxicolOncol.v30.i2.50 %T Vernolide-A Inhibits Radiation-Induced Hypoxia-Mediated Tumor Angiogenesis by Regulating HIF-1α, MMP-2, MMP-9, and VEGF %U https://www.dl.begellhouse.com/journals/0ff459a57a4c08d0,76aa57c972132785,355aeba761d57fb8.html %V 30 %X 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. %8 2011-06-22