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

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

doi:10.1186/s12885-015-1960-z

Shimin Pei, Huanan Wang + Show 5 more

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https://doi.org/10.1186/s12885-015-1960-z

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Journal: BMC Cancer	Publication Date: Dec 1, 2015
Citations: 79	License type: cc-by

Affiliation: China Agricultural University, Zhejiang University

Abstract

BackgroundMetastasis 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.MethodsWe 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.ResultsWe 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.ConclusionsOur 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1960-z) contains supplementary material, which is available to authorized users.

Highlights

Metastasis is the major cause of death in breast cancers
PMS dramatically reduced the activity of Matrix metalloproteinase 9 (MMP9) and MMP2 in vitro According to Docking calculations by SwissDock software, PMS can targeted combined to MMP9 (Fig. 1b), the affinity is strongest when ΔG = -10.39 kcal/mol
Other agent can combine to MMP9 (Additional file 1: Table S1 and Additional file 2: Figure S1), the ΔG was higher than -10 kcal/mol, which means the affinity of PMS to MMP9 was the strongest among these 11 agents

Summary

Introduction

Metastasis is the major cause of death in breast cancers. Gelatinase inhibitor can effectively suppress tumor metastasis. At present, there is no dramatically effective gelatinase inhibitor against breast cancer. Breast cancer is the most common type of malignant disease in women worldwide. In the past two decades the mortality rate in breast cancer patients has been decreasing thanks to the development of early diagnostic methods and more effective treatments. Many breast cancer patients suffer relapse and metastasis after treatment [3]. The metastasis of primary tumors depends on the characteristics of cancer cells themselves, and the formation of proper environments, which is named as “metastatic niche”. In order to cure breast cancer, the mechanism of its metastasis must be fully understood to facilitate the establishment of methods to suppress the metastasis

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Results

Conclusion