Inhibitory Effects of Isorhamnetin on the Invasion of Human Breast Carcinoma Cells by Downregulating the Expression and Activity of Matrix Metalloproteinase-2/9

被引:44
作者
Li, Chenglin [1 ]
Yang, Dan [1 ]
Zhao, Yuanwei [2 ]
Qiu, Yu [1 ]
Cao, Xin [1 ]
Yu, Yanyan [1 ]
Guo, Hao [1 ]
Gu, Xiaoke [1 ]
Yin, Xiaoxing [1 ]
机构
[1] Xuzhou Med Coll, Jiangsu Ctr Collaborat & Innovat Canc Biotherapy, Jiangsu Key Lab New Drug Res & Clin Pharm, Xuzhou, Peoples R China
[2] Peoples Hosp Pizhou, Xuzhou, Peoples R China
来源
NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL | 2015年 / 67卷 / 07期
基金
中国博士后科学基金;
关键词
CANCER CELLS; TUMOR INVASION; UP-REGULATION; KAPPA-B; MMP-9; ACTIVATION; MAPK; METASTASIS; KINASE; MATRIX-METALLOPROTEINASE-9;
D O I
10.1080/01635581.2015.1073763
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Matrix metalloproteinases (MMPs) play an active role in facilitating the invasion of cancer cells with excessive extracellular matrix (ECM) degradation. In the present study, we investigated the antiinvasive effects of isorhamnetin, a naturally occurring flavonoid, on MDA-MB-231 human breast carcinoma cells. The results indicated that isorhamnetin significantly inhibited the adhesion, migration, and invasion of the cells in vitro. Moreover, isorhamnetin suppressed the activity and expression of MMP-2 and MMP-9, which were determined by gelatin zymography, real-time PCR, and Western blot analysis, respectively. Besides, isorhamnetin had little effect on the secretion of urokinase plasminogen activator. Further elucidation of the mechanism revealed that isorhamnetin exerted an inhibitory effect on the phosphorylation of p38 and STAT3, although it had no effect on ERK1/2 and JNK. Taken together, these data demonstrated that isorhamnetin could significantly inhibit the invasion of MDA-MB-231 cells by downregulating the expression and activity of MMP-2 and MMP-9, which was potentially associated with the suppression of p38 MAPK and STAT3. Therefore, the findings provide new evidence for the anti-cancer activity of isorhamnetin.
引用
收藏
页码:1191 / 1200
页数:10
相关论文
共 48 条
[1]   Visfatin induces human endothelial VEGF and MMP-2/9 production via MAPK and PI3K/Akt signalling pathways: novel insights into visfatin-induced angiogenesis [J].
Adya, Raghu ;
Tan, Bee K. ;
Punn, Anu ;
Chen, Jing ;
Randeva, Harpal S. .
CARDIOVASCULAR RESEARCH, 2008, 78 (02) :356-365
[2]  
Albini A, 1998, Pathol Oncol Res, V4, P230
[3]   THE X-RAY CRYSTAL-STRUCTURE OF THE CATALYTIC DOMAIN OF HUMAN NEUTROPHIL COLLAGENASE INHIBITED BY A SUBSTRATE-ANALOG REVEALS THE ESSENTIALS FOR CATALYSIS AND SPECIFICITY [J].
BODE, W ;
REINEMER, P ;
HUBER, R ;
KLEINE, T ;
SCHNIERER, S ;
TSCHESCHE, H .
EMBO JOURNAL, 1994, 13 (06) :1263-1269
[4]   Axis of evil: molecular mechanisms of cancer metastasis [J].
Bogenrieder, T ;
Herlyn, M .
ONCOGENE, 2003, 22 (42) :6524-6536
[5]   Wogonoside inhibits lipopolysaccharide-induced angiogenesis in vitro and in vivo via toll-like receptor 4 signal transduction [J].
Chen, Yan ;
Lu, Na ;
Ling, Yun ;
Gao, Ying ;
Wang, Ling ;
Sun, Yu ;
Qi, Qi ;
Feng, Feng ;
Liu, Wenyuan ;
Liu, Wei ;
You, Qidong ;
Guo, Qinglong .
TOXICOLOGY, 2009, 259 (1-2) :10-17
[6]   Involvement of MAPK pathway in TNF-α-induced MMP-9 expression in human trophoblastic cells [J].
Cohen, Marie ;
Meisser, Arielle ;
Haenggeli, Luise ;
Bischof, Paul .
MOLECULAR HUMAN REPRODUCTION, 2006, 12 (04) :225-232
[7]   Requirement of matrix metalloproteinase-9 for the transformation of human mammary epithelial cells by Stat3-C [J].
Dechow, TN ;
Pedranzini, L ;
Leitch, A ;
Leslie, K ;
Gerald, WL ;
Linkov, I ;
Bromberg, JF .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (29) :10602-10607
[8]   Matrix metalloproteinases and tumor metastasis [J].
Deryugina, EI ;
Quigley, JP .
CANCER AND METASTASIS REVIEWS, 2006, 25 (01) :9-34
[9]  
Duffy MJ, 2002, CLIN CHEM, V48, P1194
[10]   Positive feedback regulation between MMP-9 and VEGF in human RPE cells [J].
Hollborn, Margrit ;
Stathopoulos, Christina ;
Steffen, Anja ;
Wiedemann, Peter ;
Kohen, Leon ;
Bringmann, Andreas .
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2007, 48 (09) :4360-4367