Hyul-Tong-Ryung suppresses PMA-induced MMP-9 expression by inhibiting AP-1-mediated gene expression via ERK1/2 signaling pathway in MCF-7 human breast cancer cells

Kyoung Sook Kim, Lan Yao, Young Choon Lee, Eunsook Chung, Kyung Mi Kim, Yeon Joo Kwak, Seok Jo Kim, Zheng Cui, Jai Heon Lee*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

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 kinase1/2 (ERK1/2) 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 kinase1/2 (ERK 1/2) signaling pathway.

Original languageEnglish (US)
Pages (from-to)600-606
Number of pages7
JournalImmunopharmacology and Immunotoxicology
Volume32
Issue number4
DOIs
StatePublished - Dec 1 2010

Keywords

  • AP-1
  • ERK 1/2 signaling pathway
  • Hyul-Tong-Ryung
  • MCF-7 cells
  • MMP-9

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Toxicology
  • Pharmacology

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