Hyul-Tong-Ryung suppresses PMA-induced MMP-9 expression by inhibiting AP-1-mediated gene expression via ERK 1/2 signaling pathway in MCF-7 human breast cancer cells.
Our previous study has demonstrated that the methanol extract of Hyul-Tong-Ryung (HM) specifically suppresses the phorbol 12-myristate 13-acetate (PMA)-induced matrix metalloproteinase-9 (MMP-9) production through the inhibition of MMP-9 mRNA expression in MCF-7 human breast carcinoma cells. However, the molecular mechanisms involved in transcriptional suppression of MMP-9 by HM in PMA-induced MCF-7 cells are not known. In this study, we aimed to elucidate the molecular mechanisms involved in the inhibition of MMP-9 expression by HM in PMA-induced MCF-7 cells. The results of promoter assay and EMSA showed that HM specifically inhibits MMP-9 gene expression by blocking PMA-stimulated activation of activator protein-1 (AP-1). In addition, PMA-stimulated phosphorylation of extracellular signal regulated kinase 1/2 (ERK 1/2) was suppressed by HM treatment, whereas the phosphorylation of either c-Jun N-terminal kinase (JNK) or p38 mitogen-activated protein kinase (MAPK) was not affected. HM could inhibit the PMA-induced MMP-9 expression through suppression of the transcriptional activity of MMP-9 gene in MCF-7 cells. These results indicate that HM inhibits PMA-induced MMP-9 expression by blocking the activation of activator protein-1 (AP-1) via extracellular signal regulated kinase 1/2 (ERK 1/2) signaling pathway.
College of Natural Resources and Life Science, BK21 Center for Silver-Bio Industrialization, Dong-A University, Busan, South Korea.
Kyoung-Sook
KS
Kim
Lan
L
Yao
Young-Choon
YC
Lee
Eunsook
E
Chung
Kyung-Mi
KM
Kim
Yeon-Joo
YJ
Kwak
Seok-Jo
SJ
Kim
Zheng
Z
Cui
Jai-Heon
JH
Lee
D001943:Breast Neoplasms / Q000473:pathology; D045744:Cell Line, Tumor; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005260:Female; D015870:Gene Expression / Q000187:drug effects* / Q000235:genetics; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D020218:Response Elements / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000378:metabolism; D014162:Transfection
D004365:Drugs, Chinese Herbal; C556342:Hyul-Tong-Ryung; D016328:NF-kappa B; D047428:Protein Kinase Inhibitors; D018808:Transcription Factor AP-1; D051996:Transcription Factor RelA; D004247:DNA; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D020780:Matrix Metalloproteinase 9; D013755:Tetradecanoylphorbol Acetate