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BMC Cancer
Published in: BMC Cancer 1/2015

Open Access 01-12-2015 | Research article

Plantamajoside, a potential anti-tumor herbal medicine inhibits breast cancer growth and pulmonary metastasis by decreasing the activity of matrix metalloproteinase-9 and -2

Authors: Shimin Pei, Xu Yang, Huanan Wang, Hong Zhang, Bin Zhou, Di Zhang, Degui Lin

Published in: BMC Cancer | Issue 1/2015

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Abstract

Background

Metastasis is the major cause of death in breast cancers. MMPs play a key role in tumor microenvironment that facilitates metastasis. The existing researches suggest that the high expression of gelatinase A and B (MMP2 and MMP9) promote the metastasis of breast cancer. Therefore, gelatinase inhibitor can effectively suppress tumor metastasis. However, at present, there is no dramatically effective gelatinase inhibitor against breast cancer.

Methods

We screened gelatinase inhibitor among Chinese herbal medicine by molecular docking technology; investigated the proliferation, migration and invasion of MDA-MB-231 human breast cancer cell line and 4T1 mouse breast cancer cell line in response to the treatment with the screened inhibitor by wound assay, invasion assay and gelatin zymography; then further examined the effects of inhibitor on allograft mammary tumors of mice by immunohistochemistry.

Results

We successfully screened an Chinese herbal medicine-Plantamajoside(PMS)-which can reduce the gelatinase activity of MMP9 and MMP2. In vitro, PMS can inhibit the proliferation, migration and invasion of MDA-MB-231 human breast cancer cell line and 4T1 mouse breast cancer cell line by decreasing MMP9 and MMP2 activity. In vivo, oral administration of PMS to the mice bearing 4T1 cells induced tumors resulted in significant reduction in allograft tumor volume and weights, significant decrease in microvascular density and significant lower lung metastasis rate.

Conclusions

Our results indicate that as a promising anti-cancer agent, PMS may inhibit growth and metastasis of breast cancer by inhibiting the activity of MMP9 and MMP2.
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Literature
1.
Filipova A, Seifrtova M, Mokry J, Dvorak J, Rezacova M, Filip S, et al. Breast cancer and cancer stem cells a mini-review. Tumori. 2014;100(4):363–9.PubMed
2.
Bohl CR, Harihar S, Denning WL, Sharma R, Welch DR. Metastasis suppressors in breast cancers: mechanistic insights and clinical potential. J Mol Med. 2014;92(1):13–30.PubMedCentralPubMedCrossRef
3.
Gaffan J, Dacre J, Jones A. Educating undergraduate medical students about oncology: a literature review. J Clin Oncol. 2006;24:1932–9.PubMedCrossRef
4.
Bethan P, David L. The metastatic niche: adapting the foreign soil. Nat Rev Cancer. 2009;9(4):285–93.CrossRef
5.
Kohrmann A, Kammerer U, Kapp M, Dietl J, Anacker J. Expression of matrix metalloproteinases (MMPs) in primary human breast cancer and breast cancer cell lines: new findings and review of the literature. BMC Cancer. 2009;9:188.PubMedCentralPubMedCrossRef
6.
7.
Chabottaux V, Noel A. Breast cancer progression: insights into multifaceted matrix metalloproteinases. Clin Exp Metastasis. 2007;24(8):647–56.PubMedCrossRef
8.
Talvensaari-Mattila A, Turpeenniemi-Hujanen T. Preoperative serum MMP-9 immunoreactive protein is a prognostic indicator for relapse-free survival in breast carcinoma. Cancer Lett. 2005;217(2):237–42.PubMedCrossRef
9.
Wu ZS, Wu Q, Yang JH, Wang HQ, Ding XD, Yang F, et al. Prognostic significance of MMP-9 and TIMP-1 serum and tissue expression in breast cancer. Int J Cancer. 2008;122(9):2050–6.PubMedCrossRef
10.
Mehner C, Hockla A, Miller E, Ran S, Radisky DC, Radisky ES. Tumor cell-produced matrix metalloproteinase 9 (MMP-9) drives malignant progression and metastasis of basal-like triple negative breast cancer. Oncotarget. 2014;5(9):2736–49.PubMedCentralPubMedCrossRef
11.
Puzovic V, Brcic I, Ranogajec I, Jakic-Razumovic J. Prognostic values of ETS-1, MMP-2 and MMP-9 expression and co-expression in breast cancer patients. Neoplasma. 2014;61(4):439–46.PubMedCrossRef
12.
Min KW, Kim DH, Do SI, Kim K, Lee HJ, Chae SW, et al. Expression patterns of stromal MMP-2 and tumoural MMP-2 and -9 are significant prognostic factors in invasive ductal carcinoma of the breast. APMIS. 2014;122(12):1196–206.PubMedCrossRef
13.
Niemiec J, Adamczyk A, Malecki K, Ambicka A, Rys J. Tumor grade and matrix metalloproteinase 2 expression in stromal fibroblasts help to stratify the high-risk group of patients with early breast cancer identified on the basis of st Gallen recommendations. Clin Breast Cancer. 2013;13(2):119–28.PubMedCrossRef
14.
Artacho-Cordon F, Rios-Arrabal S, Lara PC, Artacho-Cordon A, Calvente I, Nunez MI. Matrix metalloproteinases: potential therapy to prevent the development of second malignancies after breast radiotherapy. Surg Oncol. 2012;21(3):e143–151.PubMedCrossRef
15.
Chinese traditional Chinese medicine academic yearbook Academic volume. Shanghai University of Traditional Chinese Medicine Press. 2012;12:239-241.
16.
Kitchen DB, Decornez H, Furr JR, Bajorath J. Docking and scoring in virtual screening for drug discovery: methods and applications. Nat Rev Drug Discov. 2004;3(11):935–49.PubMedCrossRef
17.
Doan DD, Nguyen NH, Doan HK, Nguyen TL, Phan TS, van Dau N, et al. Studies on the individual and combined diuretic effects of four Vietnamese traditional herbal remedies (Zea mays, Imperata cylindrica, Plantago major and Orthosiphon stamineus). J Ethnopharmacol. 1992;36(3):225–31.PubMedCrossRef
18.
Li Y, Gan L, Li GQ, Deng L, Zhang X, Deng Y. Pharmacokinetics of plantamajoside and acteoside from Plantago asiatica in rats by liquid chromatography-mass spectrometry. J Pharm Biomed Anal. 2014;89:251–6.PubMedCrossRef
19.
Jung HY, Seo DW, Hong CO, Kim JY, Yang SY, Lee KW. Nephroprotection of plantamajoside in rats treated with cadmium. Environ Toxicol Pharmacol. 2015;39(1):125–36.PubMedCrossRef
20.
Damery S, Gratus C, Grieve R, Warmington S, Jones J, Routledge P, et al. The use of herbal medicines by people with cancer: a cross-sectional survey. Br J Cancer. 2011;104(6):927–33.PubMedCentralPubMedCrossRef
21.
Zhang J, Wang P, Ouyang H, Yin J, Liu A, Ma C, et al. Targeting cancer-related inflammation: Chinese herbal medicine inhibits epithelial-to-mesenchymal transition in pancreatic cancer. PLoS ONE. 2013;8(7):e70334.PubMedCentralPubMedCrossRef
22.
23.
Nagalingam A, Kuppusamy P, Singh SV, Sharma D, Saxena NK. Mechanistic elucidation of the antitumor properties of withaferin a in breast cancer. Cancer Res. 2014;74(9):2617–29.PubMedCentralPubMedCrossRef
24.
Safarzadeh E, Sandoghchian Shotorbani S, Baradaran B. Herbal medicine as inducers of apoptosis in cancer treatment. Adv Pharm Bull. 2014;4 Suppl 1:421–7.PubMedCentralPubMed
25.
Xia H, JIn G, Sun l, Yang J. Research Progress on chemical constituents and pharmacological effects of plantain. China Pharm. 2013;16(2):294–6.
26.
Choi SY, Jung SH, Lee HS, Park KW, Yun BS, Lee KW. Glycation inhibitory activity and the identification of an active compound in Plantago asiatica extract. Phytother Res. 2008;22(3):323–9.PubMedCrossRef
27.
28.
Wang X, Lu H, Urvalek AM, Li T, Yu L, Lamar J, et al. KLF8 promotes human breast cancer cell invasion and metastasis by transcriptional activation of MMP9. Oncogene. 2011;30(16):1901–11.PubMedCentralPubMedCrossRef
29.
Arnold S, Mira E, Muneer S, Korpanty G, Beck AW, Holloway SE, et al. Forced expression of MMP9 rescues the loss of angiogenesis and abrogates metastasis of pancreatic tumors triggered by the absence of host SPARC. Exp Biol Med (Maywood). 2008;233(7):860–73.CrossRef
30.
Pulaski BA, Ostrand-Rosenberg S. Reduction of established spontaneous mammary carcinoma metastases following immunotherapy with major histocompatibility complex class II and B7.1 cell-based tumor vaccines. Cancer Res. 1998;58:1486–93.PubMed
31.
Lelekakis M, Moseley J, Martin T, Hards D, Williams E, Ho P, et al. A novel orthotopic model of reast cancer metastasis to bone. Clin Exp Metastasis. 1999;17:163–70.PubMedCrossRef
32.
Bao L, Haque A, Jackson K, Hazari S, Moroz K, Jetly R, et al. Increased expression of P-glycoprotein is associated with doxorubicin chemoresistance in the metastatic 4T1 breast cancer model. Am J Pathol. 2011;178(2):838–52.PubMedCentralPubMedCrossRef
33.
Pharmacology experiment methodology. People’s Medical Publishing House 2002.
34.
Li LI, Chunming LIU, Zhaojie CHEN, Jing WANG, Dong-fang SHI, Zhi-qiang LIU. Isolation and purification of plantamajoside and acteoside from plant extract of plantago asiatica L. by high performance centrifugal partition chromatography. Chem Res Chinese Universities. 2009;25(6):817–21.
35.
Park BG, Lee HS, Jung SH, Hong CO, Won HJ, Park HY, et al. A 90 day repeated oral toxicity study on plantamajoside concentrate from Plantago asiatica. Phytother Res. 2007;21(12):1118–23.PubMedCrossRef
36.
37.
Gao D, Nolan DJ, Mellick AS, Bambino K, McDonnell K, Mittal V. Endothelial progenitor cells control the angiogenic switch in mouse lung metastasis. Science. 2008;319(11):195–8.PubMedCrossRef
38.
Kang Y, Siegel PM, Shu W, Drobnjak M, Kakonen SM, Cordón-Cardo C, et al. A multigenic program mediating breast cancer metastasis to bone. Cancer Cell. 2003;3(6):537–49.PubMedCrossRef
39.
Wu X, Zhang Y, Pei Z, Chen S, Yang X, Chen Y, et al. Methylseleninic acid restricts tumor growth in nude mice model of metastatic breast cancer probably via inhibiting angiopoietin-2. BMC Cancer. 2012;12(192):1471–2407.
Metadata
Title
Plantamajoside, a potential anti-tumor herbal medicine inhibits breast cancer growth and pulmonary metastasis by decreasing the activity of matrix metalloproteinase-9 and -2
Authors
Shimin Pei
Xu Yang
Huanan Wang
Hong Zhang
Bin Zhou
Di Zhang
Degui Lin
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2015
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-015-1960-z

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