title: Chrysin inhibits tumor promoter-induced MMP-9 expression by blocking AP-1 via suppression of ERK and JNK pathways in gastric cancer cells.
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.
authors: Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors: Yong
authors: Y
authors: Xia
authors: Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors: Sen
authors: S
authors: Lian
authors: Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors: Pham Ngoc
authors: PN
authors: Khoi
authors: Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors: Hyun Joong
authors: HJ
authors: Yoon
authors: Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors: Young Eun
authors: YE
authors: Joo
authors: Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors: Kee Oh
authors: KO
authors: Chay
authors: Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors: Kyung Keun
authors: KK
authors: Kim
authors: Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors: Young
authors: Y
authors: Do Jung
mesh_terms: D000906:Antibodies / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005419:Flavonoids / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000235:genetics* / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D048055:Mitogen-Activated Protein Kinase 8 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D048056:Mitogen-Activated Protein Kinase 9 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013270:Stomach / Q000187:drug effects / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism
chemical_list: D000906:Antibodies; D000972:Antineoplastic Agents, Phytogenic; D005419:Flavonoids; D009838:Oligodeoxyribonucleotides; D016760:Proto-Oncogene Proteins c-fos; D018808:Transcription Factor AP-1; C043561:chrysin; D048056:Mitogen-Activated Protein Kinase 9; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048055:Mitogen-Activated Protein Kinase 8; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; D013755:Tetradecanoylphorbol Acetate