Octacosanol isolated from Tinospora cordifolia downregulates VEGF gene expression by inhibiting nuclear translocation of NF-<kappa>B and its DNA binding activity.
Octacosanol is a long-chain aliphatic alcohol, which is the main component of policosanol used as a normolipidemic agent. It is known that angiogenesis is involved in tumor growth and metastasis. The present study identified octacosanol isolated from the plant Tinospora cordifolia as a new antiangiogenic compound with inhibitory effects on in vivo angiogenesis assays. Our results showed that octacosanol (i) inhibits proliferation of endothelial cells and Ehrlich ascites tumor cells, (ii) inhibits neovascularization induced by angiogenic factors in chick chorioallantoic membrane and rat cornea in vivo angiogenesis assays, (iii) inhibits secretion of ascites fluid in the growing tumor cells in vivo. Concerning the mechanism of action, octacosanol inhibited secretion of vascular endothelial growth factor into ascites fluid by the tumor cells. At the molecular level octacosanol markedly inhibits activity of matrix metalloproteinases (MMPs) and translocation of transcription factor nuclear factor-<kappa>B to nucleus. The mechanism of inhibition of angiogenesis by octacosanol reflects on its effect on tumor angiogenesis and metastasis.
Thippeswamy
G
G
Department of Studies in Applied Botany and Biotechnology, University of Mysore, Manasagangotri, Mysore-570006, India.
Sheela
M L
ML
Salimath
Bharathi P
BP
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy; D002467:Cell Nucleus / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002645:Chickens; D004247:DNA / Q000378:metabolism*; D015536:Down-Regulation; D005233:Fatty Alcohols / Q000494:pharmacology*; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D031610:Tinospora / Q000737:chemistry*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000235:genetics
D020533:Angiogenesis Inhibitors; D005233:Fatty Alcohols; D061965:Matrix Metalloproteinase Inhibitors; D016328:NF-kappa B; D042461:Vascular Endothelial Growth Factor A; C044309:1-octacosanol; D004247:DNA