Myricetin suppresses breast cancer metastasis through down-regulating the activity of matrix metalloproteinase (MMP)-2/9

被引:91
作者
Ci, Yingqian [1 ]
Zhang, Yubo [1 ]
Liu, Yanjie [2 ]
Lu, Shuai [1 ]
Cao, Jianhua [1 ]
Li, Huajun [1 ]
Zhang, Jing [1 ]
Huang, Zongyu [1 ]
Zhu, Xudong [2 ]
Gao, Jin [3 ]
Han, Mei [1 ]
机构
[1] Beijing Normal Univ, Coll Chem, Key Lab Radiopharmaceut, Minist Educ, Beijing, Peoples R China
[2] Beijing Normal Univ, Coll Life Sci, Beijing, Peoples R China
[3] Anhui Med Univ, Dept Radiat Oncol, Anhui Prov Hosp, Hefei, Anhui, Peoples R China
关键词
breast cancer; metastasis; MMP-2; 9; Myricetin; ST6GALNAC5; EXPRESSION; CELLS; ABILITY;
D O I
10.1002/ptr.6071
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Tumour metastasis is the major cause of breast cancer mortality. Myricetin, a natural polyphenol, is found in teas, wines, and berries. The pharmacodynamic action and molecular mechanism of myricetin on breast cancer metastasis remain unknown. Here, we investigated the effect of myricetin on MDA-Mb-231Br cell viability, migration, invasion, and 4T1 mouse lung metastasis mouse models. MMP-2/9 protein expression and ST6GALNAC5 expression were analysed using western blot assays and quantitative real-time polymerase chain reaction, respectively. Cell migration and invasion were detected by wound-healing and Boyden transwell assays. The antimetastatic effect in vivo was evaluated by lung metastasis model. Myricetin significantly decreased the activities of MMP-2/9 and mRNA levels of ST6GALNAC5. In addition, the migration, invasion, and adhesion were effectively inhibited in a concentration-dependent manner. On the other hand, mice treated with myricetin exhibited smaller tumour nodules compared with the vehicle mice, with only 17.78 +/- 15.41% after treatment with 50mg/kg myricetin. In conclusion, myricetin could significantly block invasion of MDA-Mb-231Br cells through suppressing the protein expression of MMP-2/9 and the expression of ST6GALNAC5, as well as lung metastasis in a mouse model, which suggests that myricetin should be developed as a potential therapeutic candidate for breast cancer.
引用
收藏
页码:1373 / 1381
页数:9
相关论文
共 35 条
[1]  
American Cancer Society, 2015, CANC FACTS FIGS, P2015
[2]   Potential therapeutic antioxidants that combine the radical scavenging ability of myricetin and the lipophilic chain of vitamin E to effectively inhibit microsomal lipid peroxidation [J].
Bennett, CJ ;
Caldwell, ST ;
McPhail, DB ;
Morrice, PC ;
Duthie, GG ;
Hartley, RC .
BIOORGANIC & MEDICINAL CHEMISTRY, 2004, 12 (09) :2079-2098
[3]   Genes that mediate breast cancer metastasis to the brain [J].
Bos, Paula D. ;
Zhang, Xiang H. -F. ;
Nadal, Cristina ;
Shu, Weiping ;
Gomis, Roger R. ;
Nguyen, Don X. ;
Minn, Andy J. ;
van de Vijver, Marc J. ;
Gerald, William L. ;
Foekens, John A. ;
Massague, Joan .
NATURE, 2009, 459 (7249) :1005-U137
[4]   Inhibitory effects of wogonin on the invasion of human breast carcinoma cells by downregulating the expression and activity of matrix metalloproteinase-9 [J].
Chen, Pu ;
Lu, Na ;
Ling, Yun ;
Chen, Yan ;
Hui, Hui ;
Lu, Zhijian ;
Song, Xiuming ;
Li, Zhiyu ;
You, Qidong ;
Guo, Qinglong .
TOXICOLOGY, 2011, 282 (03) :122-128
[5]   Cancer Statistics in China, 2015 [J].
Chen, Wanqing ;
Zheng, Rongshou ;
Baade, Peter D. ;
Zhang, Siwei ;
Zeng, Hongmei ;
Bray, Freddie ;
Jemal, Ahmedin ;
Yu, Xue Qin ;
He, Jie .
CA-A CANCER JOURNAL FOR CLINICIANS, 2016, 66 (02) :115-132
[6]   Contribution of reactive oxygen species to migration/invasion of human glioblastoma cells U87 via ERK-dependent COX-2/PGE2 activation [J].
Chiu, Wen-Ta ;
Shen, Shing-Chuan ;
Chow, Jyh-Ming ;
Lin, Cheng-Wei ;
Shia, Ling-Tin ;
Chen, Yen-Chou .
NEUROBIOLOGY OF DISEASE, 2010, 37 (01) :118-129
[7]   Molecular Mechanisms and Metabolomics of Natural Polyphenols Interfering with Breast Cancer Metastasis [J].
Ci, Yingqian ;
Qiao, Jinping ;
Han, Mei .
MOLECULES, 2016, 21 (12)
[8]   Inhibition of silibinin on migration and adhesion capacity of human highly metastatic breast cancer cell line, MDA-MB-231, by evaluation of β1-integrin and downstream molecules, Cdc42, Raf-1 and D4GDI [J].
Dastpeyman, Mohadeseh ;
Motamed, Nasrin ;
Azadmanesh, Kayhan ;
Mostafavi, Ehsan ;
Kia, Vahid ;
Jahanian-Najafabadi, Ali ;
Shokrgozar, Mohammad Ali .
MEDICAL ONCOLOGY, 2012, 29 (04) :2512-2518
[9]   Treatment of breast cancer brain metastases [J].
Freedman R.A. ;
Anders C.K. .
Current Breast Cancer Reports, 2012, 4 (1) :1-9
[10]   Dual Action of Myricetin on Porphyromonas gingivalis and the Inflammatory Response of Host Cells: A Promising Therapeutic Molecule for Periodontal Diseases [J].
Grenier, Daniel ;
Chen, Huangqin ;
Ben Lagha, Amel ;
Fournier-Larente, Jade ;
Morin, Marie-Pierre .
PLOS ONE, 2015, 10 (06)