Beta-eudesmol suppresses tumour growth through inhibition of tumour neovascularisation and tumour cell proliferation.
In the present study, we investigated the potential anti-angiogenic mechanism and anti-tumour activity of beta-eudesmol using in vitro and in vivo experimental models. Proliferation of human umbilical vein endothelial cells (HUVEC) stimulated with vascular endothelial growth factor (VEGF, 30 ng/ml) and basic fibroblast growth factor (bFGF, 30 ng/ml) was significantly inhibited by beta-eudesmol (50-100 microM). Beta-eudesmol (100 microM) also blocked the phosphorylation of cAMP response element binding protein (CREB) induced by VEGF (30 ng/ml) in HUVEC. Beta-eudesmol (10-100 microM) inhibited proliferation of HeLa, SGC-7901, and BEL-7402 tumour cells in a time- and dose-dependent manner. Moreover, beta-eudesmol treatment (2.5-5 mg/kg) significantly inhibited growth of H(22) and S(180) mouse tumour in vivo. These results indicated that beta-eudesmol inhibited angiogenesis by suppressing CREB activation in growth factor signalling pathway. This is the first study to demonstrate that beta-eudesmol is an inhibitor of tumour growth.
Ma
En-Long
EL
Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, China. maenlong@hotmail.com
Li
Yan-Chun
YC
Tsuneki
Hiroshi
H
Xiao
Jin-Fang
JF
Xia
Ming-Yu
MY
Wang
Min-Wei
MW
Kimura
Ikuko
I
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006801:Humans; D008297:Male; D051379:Mice; D015394:Molecular Structure; D009369:Neoplasms / Q000098:blood supply* / Q000188:drug therapy* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D010766:Phosphorylation; D008517:Phytotherapy; D045787:Sesquiterpenes, Eudesmane / Q000494:pharmacology* / Q000627:therapeutic use; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
D000972:Antineoplastic Agents, Phytogenic; D017362:Cyclic AMP Response Element-Binding Protein; D045787:Sesquiterpenes, Eudesmane; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; C051082:beta-eudesmol