Quercetin, a dietary-derived flavonoid, possesses antiangiogenic potential

被引:158
作者
Tan, WF [1 ]
Lin, LP [1 ]
Li, MH [1 ]
Zhang, YX [1 ]
Tong, YG [1 ]
Xiao, D [1 ]
Ding, J [1 ]
机构
[1] Chinese Acad Sci, Shanghai Inst Biol Sci, Div Antitumor Pharmacol, State Key Lab Drug Res,Shanghai Inst Mat Med, Shanghai 200031, Peoples R China
关键词
quercetin; angiogenesis; umbilical vein endothelial cell; (Human); microvascular dermal endothelial cell; matrix metalloproteinase-2;
D O I
10.1016/S0014-2999(02)02848-0
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Quercetin, a dietary-derived flavonoid, suppresses tumor growth in vitro and in vivo, and inhibits the activity of tyrosine kinase. The effects of quercetin on the angiogenic process were examined in this study. Quercetin was found to inhibit several important steps of angiogenesis including proliferation, migration, and tube formation of human microvascular dermal enclothelial cells in a dose-dependent manner. Additionally, the effect of quercetin on endothelial cell proliferation was confirmed using human umbilical vein endothelial cells. The activity of quercetin on the proliferation of endothelial cells was stronger than that on A549, BEL-7402, MKN-45 tumor cells and NIH-3T3 fibroblast cells. The chicken chorioallantoic membrane assay revealed that addition of quercetin displayed an antiangiogenic effect in vivo. After exposure to quercetin. a decrease in the expression and activity of matrix metalloproteinase-2, which is involved in the angiogenic process of migration, invasion, and tube formation, was observed by reverse transcription-polymerase chain reaction (RT-PCR) and gelatin zymography. These findings suggest that quercetin has antiangiogenic potential and that this effect may be related to an influence on the expression and activity of matrix metalloproteinase-2. (C) 2002 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:255 / 262
页数:8
相关论文
共 36 条
[1]   Inhibition of endothelial cell migration, intercellular communication, and vascular tube formation by thromboxane A2 [J].
Ashton, AW ;
Yokota, R ;
John, G ;
Zhao, SM ;
Suadicani, SO ;
Spray, DC ;
Ware, JA .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (50) :35562-35570
[2]  
BATTEGAY EJ, 1995, J MOL MED, V73, P333
[3]   THE EFFECTS OF THE BIOFLAVONOID QUERCETIN ON SQUAMOUS-CELL CARCINOMA OF HEAD AND NECK ORIGIN [J].
CASTILLO, MH ;
PERKINS, E ;
CAMPBELL, JH ;
DOERR, R ;
HASSETT, JM ;
KANDASWAMI, C ;
MIDDLETON, E .
AMERICAN JOURNAL OF SURGERY, 1989, 158 (04) :351-355
[4]   INTERFERENCE OF SOME FLAVONOIDS AND NON-STEROIDAL ANTI-INFLAMMATORY DRUGS WITH OXIDATIVE-METABOLISM OF ARACHIDONIC-ACID BY HUMAN-PLATELETS AND NEUTROPHILS [J].
CORVAZIER, E ;
MACLOUF, J .
BIOCHIMICA ET BIOPHYSICA ACTA, 1985, 835 (02) :315-321
[5]   Matrix metalloproteinase-2 is required for the switch to the angiogenic phenotype in a tumor model [J].
Fang, JM ;
Shing, Y ;
Wiederschain, D ;
Yan, L ;
Butterfield, C ;
Jackson, G ;
Harper, J ;
Tamvakopoulos, G ;
Moses, MA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (08) :3884-3889
[6]  
Ferry DR, 1996, CLIN CANCER RES, V2, P659
[7]   Intake of specific carotenoids and flavonoids and the risk of gastric cancer in Spain [J].
Garcia-Closas, R ;
Gonzalez, CA ;
Agudo, A ;
Riboli, E .
CANCER CAUSES & CONTROL, 1999, 10 (01) :71-75
[8]   Angiogenesis: New targets for the development of anticancer chemotherapies [J].
Gourley, M ;
Williamson, JS .
CURRENT PHARMACEUTICAL DESIGN, 2000, 6 (04) :417-439
[9]   DISPOSITION OF QUERCETIN IN MAN AFTER SINGLE ORAL AND INTRAVENOUS DOSES [J].
GUGLER, R ;
LESCHIK, M ;
DENGLER, HJ .
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY, 1975, 9 (2-3) :229-234
[10]   FLAVONOIDS, A CLASS OF NATURAL-PRODUCTS OF HIGH PHARMACOLOGICAL POTENCY [J].
HAVSTEEN, B .
BIOCHEMICAL PHARMACOLOGY, 1983, 32 (07) :1141-1148