1. Chrysin inhibits tumor promoter-induced MMP-9 expression by blocking AP-1 via suppression of ERK and JNK pathways in gastric cancer cells.
- Author
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Xia Y, Lian S, Khoi PN, Yoon HJ, Joo YE, Chay KO, Kim KK, and Do Jung Y
- Subjects
- Antibodies pharmacology, Cell Line, Tumor, Cell Movement drug effects, Dose-Response Relationship, Drug, Epithelial Cells metabolism, Epithelial Cells pathology, Gastric Mucosa metabolism, Humans, Matrix Metalloproteinase 9 metabolism, Mitogen-Activated Protein Kinase 1 antagonists & inhibitors, Mitogen-Activated Protein Kinase 1 genetics, Mitogen-Activated Protein Kinase 1 metabolism, Mitogen-Activated Protein Kinase 3 antagonists & inhibitors, Mitogen-Activated Protein Kinase 3 genetics, Mitogen-Activated Protein Kinase 3 metabolism, Mitogen-Activated Protein Kinase 8 antagonists & inhibitors, Mitogen-Activated Protein Kinase 8 genetics, Mitogen-Activated Protein Kinase 8 metabolism, Mitogen-Activated Protein Kinase 9 antagonists & inhibitors, Mitogen-Activated Protein Kinase 9 genetics, Mitogen-Activated Protein Kinase 9 metabolism, Oligodeoxyribonucleotides genetics, Oligodeoxyribonucleotides metabolism, Phosphorylation, Proto-Oncogene Proteins c-fos genetics, Proto-Oncogene Proteins c-fos metabolism, Signal Transduction, Stomach drug effects, Stomach pathology, Tetradecanoylphorbol Acetate antagonists & inhibitors, Tetradecanoylphorbol Acetate pharmacology, Transcription Factor AP-1 antagonists & inhibitors, Transcription Factor AP-1 metabolism, Antineoplastic Agents, Phytogenic pharmacology, Epithelial Cells drug effects, Flavonoids pharmacology, Gene Expression Regulation, Neoplastic, Matrix Metalloproteinase 9 genetics, Transcription Factor AP-1 genetics
- Abstract
Cell invasion is a crucial mechanism of cancer metastasis and malignancy. Matrix metalloproteinase-9 (MMP-9) is an important proteolytic enzyme involved in the cancer cell invasion process. High expression levels of MMP-9 in gastric cancer positively correlate with tumor aggressiveness and have a significant negative correlation with patients' survival times. Recently, mechanisms suppressing MMP-9 by phytochemicals have become increasingly investigated. Chrysin, a naturally occurring chemical in plants, has been reported to suppress tumor metastasis. However, the effects of chrysin on MMP-9 expression in gastric cancer have not been well studied. In the present study, we tested the effects of chrysin on MMP-9 expression in gastric cancer cells, and determined its underlying mechanism. We examined the effects of chrysin on MMP-9 expression and activity via RT-PCR, zymography, promoter study, and western blotting in human gastric cancer AGS cells. Chrysin inhibited phorbol-12-myristate 13-acetate (PMA)-induced MMP-9 expression in a dose-dependent manner. Using AP-1 decoy oligodeoxynucleotides, we confirmed that AP-1 was the crucial transcriptional factor for MMP-9 expression. Chrysin blocked AP-1 via suppression of the phosphorylation of c-Jun and c-Fos through blocking the JNK1/2 and ERK1/2 pathways. Furthermore, AGS cells pretreated with PMA showed markedly enhanced invasiveness, which was partially abrogated by chrysin and MMP-9 antibody. Our results suggest that chrysin may exert at least part of its anticancer effect by controlling MMP-9 expression through suppression of AP-1 activity via a block of the JNK1/2 and ERK1/2 signaling pathways in gastric cancer AGS cells.
- Published
- 2015
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