β-Eudesmol suppresses tumour growth through inhibition of tumour neovascularisation and tumour cell proliferation

被引:46
作者
Ma, En-Long [1 ]
Li, Yan-Chun [1 ]
Tsuneki, Hiroshi [2 ]
Xiao, Jin-Fang [1 ]
Xia, Ming-Yu [1 ]
Wang, Min-Wei [1 ]
Kimura, Ikuko [2 ]
机构
[1] Shenyang Pharmaceut Univ, Dept Pharmacol, Shenyang 110016, Peoples R China
[2] Toyama Med & Pharmaceut Univ, Dept Clin Pharmacol, Toyama 9300194, Japan
关键词
angiogenesis; growth factor; tumour; CREB; HUVEC;
D O I
10.1080/10286020701394332
中图分类号
Q94 [植物学];
学科分类号
071001 ;
摘要
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 mu M). beta-Eudesmol (100 mu M) also blocked the phosphorylation of cAMP response element binding protein (CREB) induced by VEGF (30 ng/ml) in HUVEC. beta-Eudesmol (10-100 mu M) 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.
引用
收藏
页码:159 / 167
页数:9
相关论文
共 14 条
[1]   Recent advances in angiogenesis, anti-angiogenesis and vascular targeting [J].
Bikfalvi, A ;
Bicknell, R .
TRENDS IN PHARMACOLOGICAL SCIENCES, 2002, 23 (12) :576-582
[2]   Angiogenesis in cancer and other diseases [J].
Carmeliet, P ;
Jain, RK .
NATURE, 2000, 407 (6801) :249-257
[3]   Vascular endothelial growth factor is essential for corpus luteum angiogenesis [J].
Ferrara, N ;
Chen, H ;
Davis-Smyth, T ;
Gerber, HP ;
Nguyen, TN ;
Peers, D ;
Chisholm, V ;
Hillan, KJ ;
Schwall, RH .
NATURE MEDICINE, 1998, 4 (03) :336-340
[4]  
FOLKMAN J, 1992, J BIOL CHEM, V267, P10931
[5]   ANGIOGENESIS IN CANCER, VASCULAR, RHEUMATOID AND OTHER DISEASE [J].
FOLKMAN, J .
NATURE MEDICINE, 1995, 1 (01) :27-31
[6]  
Kobayashi S, 1998, BIOL PHARM BULL, V21, P346, DOI 10.1248/bpb.21.346
[7]   Angiogenesis: regulators and clinical applications [J].
Liekens, S ;
De Clercq, E ;
Neyts, J .
BIOCHEMICAL PHARMACOLOGY, 2001, 61 (03) :253-270
[8]   Vascular endothelial cell growth factor activates CRE-binding protein by signaling through the KDR receptor tyrosine kinase [J].
Mayo, LD ;
Kessler, KM ;
Pincheira, R ;
Warren, RS ;
Donner, DB .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (27) :25184-25189
[9]   β-eudesmol induces neurite outgrowth in rat pheochromocytoma cells accompanied by an activation of mitogen-activated protein kinase [J].
Obara, Y ;
Aoki, T ;
Kusano, M ;
Ohizumi, Y .
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2002, 301 (03) :803-811
[10]   Mechanisms of normal and tumor-derived angiogenesis [J].
Papetti, M ;
Herman, IM .
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 2002, 282 (05) :C947-C970