Studies On Anti-angiogenic And Anti-tumor Effect By β-Eudesmol

Abnormal angiogenesis is implicated in various diseases including cancer and diabetic retinopathy. In this study, we examined the effect ofβ-eudesmol, asesquiterpenoid alcohol isolated from Atractylodes lancea rhizome, on angiogenesis in vitro and in vivo.At the uncytotoxic concentration,β-eudesmol (50-100μM) inhibited proliferation of porcine brain microvascular endothelial cells, human umbilicalvein endothelial cells (HUVEC) and human dermal microvascular endothelial cells, however, proliferation of rat aortic smooth muscle cells and rat astrocytes was not inhibited byβ-eudesmol.β-eudesmol (50-100μM) also inhibited the HUVEC migration stimulated by basic fibroblast growth factor (bFGF) and the tube formation of HUVEC in Matrigel, but did not influence the adhesion of HUVEC to fibronectin which is a component of extracellular matrix. In two in vivo angiogenesis models, Matrigel angiogenesis model and Adjuvant-induced pouch granuloma angiogenesis model, angiogenesis was obviously blocked byβ-eudesmol.β-Eudesmol (50-100μM) blocked proliferation of HUVEC stimulated by bFGF or vascular endothelial growth factor. In the endothelial cells,β-eudesmol (100μM) blocked phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 induced by bFGF or vascular endothelial growth factor, and phosphorylation of cAMP response element binding protein (CREB) induced by vascular endothelial growth factor was also blocked by B-eudesmol (50-100μM). However, phosphorylation of AKT and p38 MAP kinase induced by vascular endothelial growth factor was not influenced by B-eudesmol. Moreover intrecellular calcium levels was not changed by the treatment ofβ-eudesmol. Therforce, These results indicate thatβ-eudesmol inhibits angiogenesis, at least in part, through the blockade of growth factor-ERK and growth factor-CREB signaling pathway.Finally, we investigated the effect ofβ-eudesmol on the proliferation of human tumor cells. The results suggested thatβ-eudesmol significantly inhibited proliferation of three kinds of human tumor cells, HeLa, SGC-7901 and BEL-7402 cells.β-eudesmol also showed obvious anti-tumor effect in vivo in tumor model bearing mice H22 and S₁₈₀ tumor cells. We concluded that anti-tumor effect by B-eudesmol may be produced through direct inhibition of proliferation of tumor cells and tumor angiogenesis.According to the result above, We considered thatβ-eudesmol will be a good candidate for a new angiogenesis inhibitor and may aid in the development of drugs to treat angiogenic diseases, specially tumor diseases.