Antiangiogenic effects of butyric acid involve inhibition of VEGF/KDR gene expression and endothelial cell proliferation |
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Authors: | Gururaj Anupama E Belakavadi Madesh Salimath Bharathi P |
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Institution: | (1) Department of Biochemistry, University of Mysore, Mysore, India;(2) Department of Applied Botany and Biotechnology, University of Mysore, Mysore, India |
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Abstract: | The formation of new blood vessels from pre-existing ones is required for the growth of solid tumors and for metastasis. Interaction of tumor-secreted vascular endothelial growth factor (VEGF) with its receptor(s) on endothelial cells triggers endothelial cell proliferation and migration, which facilitate tumor angiogenesis. Butyric acid (BuA), a fermentation product of dietary fibers in the colon, is shown to alter gene expression and is postulated to be anticarcinogenic. The results presented in this paper indicate that BuA can be antiangiogenic in vivo by inhibiting angiogenesis in chorioallantoic membrane assay. BuA was not cytotoxic to endothelial cells but was a potent antiproliferative agent besides being proapoptotic to endothelial cells as verified by FACS analysis. Conditioned media from BuA-treated Ehrlich ascites tumor cells showed a 30% decrease in VEGF concentration when compared with untreated cells. The decrease in VEGF mRNA and its receptor, KDR mRNA levels in EAT and endothelial cells respectively, suggests that the VEGF-KDR system of angiogenesis is the molecular target for the antiangiogenic action of BuA. |
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Keywords: | butyrate endothelial cells apoptosis angiogenic ligand-receptor gene expression antiangiogenesis |
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