Antiangiogenic effect of 2-benzoyl-phenoxy acetamide in EAT cell is mediated by HIF-1alpha and down regulation of VEGF of in-vivo.
Benzophenones and its analogues are known for wide range of biological properties. Synthetic benzophenone analogue 2-benzoyl -phenoxy acetamide (BP-1) is proven to be potent antitumor and proapoptotic activity against EAT cells in-vivo. In the present report, we studied the antiangiogenic effect of BP-1 in EAT cells induced angiogenesis. Treatment with BP-1 in-vivo was demonstrated by the down regulation of the secretion of VEGF from EAT cells and inhibition of blood vessels formation indicating the potential angioinhibitory effect of BP-1 in EAT cells. HIF-1alpha protein, a transcription factor known to be key a regulator in hypoxia-induced angiogenesis was also down regulated by BP-1. Our findings indicated that, HIF-1alpha nuclear sequestration is repressed by BP-1 through inhibition of nuclear translocation. We postulate that diminished HIF-1alpha nuclear presence and activity in BP-1 treated EAT cells could be responsible for decreased VEGF expression and antiangiogenic effects.
Prabhakar
B T
BT
Department of Studies in Applied Botany & Biotechnology, University of Mysore, Manasagangotri, Mysore 570006, India. prabhakarbt@gmail.com
Khanum
Shaukath Ara
SA
Shashikanth
S
S
Salimath
Bharathi P
BP
D000081:Acetamides / Q000494:pharmacology*; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001202:Ascitic Fluid / Q000737:chemistry; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism*; D045744:Cell Line, Tumor; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply / Q000187:drug effects*; D015536:Down-Regulation; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010537:Peritoneum / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D021381:Protein Transport / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
C523255:2-benzoyl-phenoxy acetamide; D000081:Acetamides; D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A