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Open Access Research article

Methyl jasmonate abolishes the migration, invasion and angiogenesis of gastric cancer cells through down-regulation of matrix metalloproteinase 14

Liduan Zheng12, Dan Li3, Xuan Xiang3, Ling Tong1, Meng Qi3, Jiarui Pu3, Kai Huang24 and Qiangsong Tong23*

Author affiliations

1 Department of Pathology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, 430022, Wuhan, Hubei Province, People’s Republic of China

2 Clinical Center of Human Genomic Research, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, 430022, Wuhan, Hubei Province, People’s Republic of China

3 Department of Surgery, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, 430022, Wuhan, Hubei Province, People’s Republic of China

4 Department of Cardiology, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, 430022, Wuhan, Hubei Province, People’s Republic of China

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Citation and License

BMC Cancer 2013, 13:74  doi:10.1186/1471-2407-13-74

Published: 10 February 2013

Abstract

Background

Recent evidence indicates that methyl jasmonate (MJ), a plant stress hormone, exhibits anti-cancer activity on human cancer cells. The aim of this study is to determine whether sub-cytotoxic MJ can abolish the migration, invasion and angiogenesis gastric cancer cells.

Methods

Human gastric cancer cell lines SGC-7901 and MKN-45 were treated with diverse concentrations of MJ. Cell viability, proliferation, migration, invasion and angiogenesis capabilities of cancer cells were measured by MTT colorimetry, EdU incorporation, scratch assay, matrigel invasion assay, and tube formation assay. Gene expression was detected by western blot and real-time quantitative RT-PCR. Binding of transcription factor on gene promoter was detected by chromatin immunoprecipitation.

Results

Sub-cytotoxic (0.05 to 0.2 mM) MJ attenuated the migration, invasion and angiogenesis, but not the cell viability or proliferation, of gastric cancer cells in a time- and dose-dependent manner, with down-regulation of matrix metalloproteinase 14 (MMP-14) and its downstream gene vascular endothelial growth factor. Restoration of MMP-14 expression rescued the SGC-7901 and MKN-45 cells from sub-cytotoxic MJ-inhibited migration, invasion and angiogenesis. In addition, sub-cytotoxic MJ decreased the specificity protein 1 (Sp1) expression and binding on MMP-14 promoter, while restoration of Sp1 expression rescued the cancer cells from sub-cytotoxic MJ-mediated defects in MMP-14 expression, migration, invasion and angiogenesis.

Conclusions

Sub-cytotoxic MJ attenuates the MMP-14 expression via decreasing the Sp1 expression and binding on MMP-14 promoter, thus inhibiting the migration, invasion and angiogenesis of gastric cancer cells.

Keywords:
Gastric cancer; Methyl jasmonate; Matrix metalloproteinase 14; Specificity protein 1