Antiangiogenic effects of butyric acid involve inhibition of VEGF/KDR gene expression and endothelial cell proliferation.
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.
Gururaj
Anupama E
AE
Department of Biochemistry, University of Mysore, Mysore, India.
Belakavadi
Madesh
M
Salimath
Bharathi P
BP
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D015152:Blotting, Northern; D020148:Butyric Acid / Q000494:pharmacology*; D002455:Cell Division; D002465:Cell Movement; D002469:Cell Separation; D002478:Cells, Cultured; D002642:Chick Embryo; D002823:Chorion / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D009389:Neovascularization, Pathologic; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D014471:Umbilical Veins / Q000166:cytology; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000096:biosynthesis*
D020533:Angiogenesis Inhibitors; D017077:Culture Media, Conditioned; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D020148:Butyric Acid; D040301:Vascular Endothelial Growth Factor Receptor-2