Abstract
BackgroundRecent 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.MethodsHuman 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.ResultsSub-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.ConclusionsSub-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.
Highlights
Recent evidence indicates that methyl jasmonate (MJ), a plant stress hormone, exhibits anti-cancer activity on human cancer cells
Restoration of specificity protein 1 (Sp1) rescued sub-cytotoxic MJ-mediated suppression on matrix metalloproteinase 14 (MMP-14) expression, migration, invasion and angiogenesis of gastric cancer cells Since above evidence showed that Sp1 participated in the transcriptional regulation of matrix metalloproteinases (MMPs)-14 in gastric cancer, we proposed that Sp1 might play an important role in subcytotoxic MJ-induced decrease in the migration, invasion and angiogenesis of gastric cancer cells
Since MMP-14-mediated degradation of extracellular matrix (ECM) occurs throughout the angiogenic process and contributes to vascular regression [41], we further demonstrated that sub-cytotoxic MJ attenuated the angiogenic capabilities of gastric cancer cells
Summary
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. Salicylic acid and its derivative aspirin are extensively studied as potential anti-cancer therapeutics and chemopreventive agents [6,7]. In recent years, emerging evidence has shown the anticancer effects of naturally occurring jasmonates and their synthetic derivatives [9,10]. MJ has been found to be superior to cis-jasmone and jasmonic acid in terms of cytotoxicity and induction of apoptosis in human cancer cells [11,12], suggesting that MJ is a promising agent for the development of cancer therapeutics
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