期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 588, 期 2-3, 页码 141-150出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2008.04.027
关键词
angiogenesis; octacosanol; ascites tumor; VEGF (vascular endothelial growth factor); NF-kappa B (nuclear factor-kappa B)
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. (C) 2008 Elsevier B.V. All rights reserved.
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