EGCG, a major component of green tea, inhibits tumour growth by inhibiting VEGF induction in human colon carcinoma cells

被引:259
作者
Jung, YD
Kim, MS
Shin, BA
Chay, KO
Ahn, BW
Liu, W
Bucana, CD
Gallick, GE
Ellis, LM
机构
[1] Univ Texas, MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA
[2] Univ Texas, MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA
[3] Chonnam Natl Univ, Sch Med, Res Inst Med Sci, Kwangju 501190, South Korea
关键词
epigallocatechin gallate (EGCG); vascular endothelial growth factor (VEGF); colon carcinoma; Erk-1; Erk-2; angiogenesis;
D O I
10.1054/bjoc.2000.1691
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Catechins are key components of teas that have antiproliferative properties. We investigated the effects of green tea catechins on intracellular signalling and VEGF induction in vitro in serum-deprived HT29 human colon cancer cells and in vivo on the growth of HT29 cells in nude mice. In the in vitro studies, (-)-epigallocatechin gallate (EGCG), the most abundant catechin in green tea extract, inhibited Erk-1 and Erk-2 activation in a dose-dependent manner. However, other tea catechins such as (-)-epigallocatechin (EGC), (-)-epicatechin gallate (ECG), and (-)-epicatechin (EC) did not affect Erk-1 or 2 activation at a concentration of 30 muM. EGCG also inhibited the increase of VEGF expression and promoter activity induced by serum starvation. In the in vivo studies, athymic BALB/c nude mice were inoculated subcutaneously with HT29 cells and treated with daily intraperitoneal injections of EC (negative control) or EGCG at 1.5 mg day(-1) mouse(-1) starting 2 days after tumour cell inoculation. Treatment with EGCG inhibited tumour growth (58%), microvessel density (30%), and tumour cell proliferation (27%) and increased tumour cell apoptosis (1.9-fold) and endothelial cell apoptosis (3-fold) relative to the control condition (P< 0.05 for all comparisons). EGCG may exert at least part of its anticancer effect by inhibiting angiogenesis through blocking the induction of VEGF. (C) 2001 Cancer Research Campaign http://www.bjcancer.com.
引用
收藏
页码:844 / 850
页数:7
相关论文
共 35 条
[1]   Green tea constituent epigallocatechin-3-gallate and induction of apoptosis and cell cycle arrest in human carcinoma cells [J].
Ahmad, N ;
Feyes, DK ;
Nieminen, AL ;
Agarwal, R ;
Mukhtar, H .
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1997, 89 (24) :1881-1886
[2]   Epigallocathechin-3 gallate selectively inhibits the PDGF-BB-induced intracellular signaling transduction pathway in vascular smooth muscle cells and inhibits transformation of sis-transfected NIH 3T3 fibroblasts and human glioblastoma cells (A172) [J].
Ahn, HY ;
Hadizadeh, KR ;
Seul, C ;
Yun, YP ;
Vetter, H ;
Sachinidis, A .
MOLECULAR BIOLOGY OF THE CELL, 1999, 10 (04) :1093-1104
[3]  
Akagi Y, 1998, CANCER RES, V58, P4008
[4]   Effect of (-)-epigallocatechin gallate on leukemic blast cells from patients with acute myeloblastic leukemia [J].
Asano, Y ;
Okamura, S ;
Ogo, T ;
Eto, T ;
Otsuka, T ;
Niho, Y .
LIFE SCIENCES, 1996, 60 (02) :135-142
[5]   Angiogenesis inhibited by drinking tea [J].
Cao, YH ;
Cao, RH .
NATURE, 1999, 398 (6726) :381-381
[6]   HOW MAP KINASES ARE REGULATED [J].
COBB, MH ;
GOLDSMITH, EJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (25) :14843-14846
[7]  
DAVIS RJ, 1993, J BIOL CHEM, V268, P14553
[8]   Down-regulation of vascular endothelial growth factor in hunan colon carcinoma cell lines by antisense transfection decreases endothelial cell proliferation [J].
Ellis, LM ;
Liu, WB ;
Wilson, M .
SURGERY, 1996, 120 (05) :871-878
[9]   Down-regulation of vascular endothelial growth factor in a human colon carcinoma cell line transfected with an antisense expression vector specific for c-src [J].
Ellis, LM ;
Staley, CA ;
Liu, WB ;
Fleming, RYD ;
Parikh, NU ;
Bucana, CD ;
Gallick, GE .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (02) :1052-1057
[10]   ANGIOGENESIS IN CANCER, VASCULAR, RHEUMATOID AND OTHER DISEASE [J].
FOLKMAN, J .
NATURE MEDICINE, 1995, 1 (01) :27-31