Inhibitory effects of a benz[f]indole-4,9-dione analog on cancer cell metastasis mediated by the down-regulation of matrix metalloproteinase expression in human HT1080 fibrosarcoma cells

Hyen Joo Park, Hyun Jung Lee, Hye Young Min, Hwa Jin Chung, Myung Eun Suh, Hye Young Park-Choo, Choonmi Kim, Hwa Jung Kim, Eun Kyung Seo, Sang Kook Lee

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17 Scopus citations

Abstract

In our previous study, a synthetic benz[f]indole-4,9-dione analog, 2-amino-3-ethoxycarbonyl-N-methylbenz[f]indole-4,9-dione (SME-6), exhibited a potential anti-tumor activity. We, in this study, further explored the anti-metastatic and anti-invasive effect of SME-6 by determining the regulation of matrix metalloproteinases (MMPs). MMPs, zinc-dependent proteolytic enzymes, play a pivotal role in tumor metastasis by cleavage of extracellular matrix as well as non-matrix substrates. On this line, we examined the influence of SME-6 on the expressions of MMP-2, -9, membrane type 1-MMP (MT1-MMP), tissue inhibitor of metalloproteinases (TIMP-1, -2), and in vitro invasiveness of human fibrosarcoma cells. Dose-dependent suppressions of MMPs and TIMP-2 mRNA levels were observed in SME-6-treated HT1080 human fibrosarcoma cells detected by reverse transcriptase-polymerase chain reaction. TIMP-1 mRNA level, however, was induced in a dose-dependent manner. Gelatin zymographic analysis also exhibited a significant down-regulation of MMP-2 and -9 expression in HT1080 cells treated with SME-6 compared to controls. Furthermore, SME-6 inhibited the invasion, motility, and migration of tumor cells. Taken together, these data provide a possible role of SME-6 as a potential antitumor agent with the markedly inhibition of the metastatic and invasive capacity of malignant cells.

Original languageEnglish
Pages (from-to)31-36
Number of pages6
JournalEuropean Journal of Pharmacology
Volume527
Issue number1-3
DOIs
StatePublished - 19 Dec 2005

Keywords

  • 2-Amino-3-ethoxycarbonyl-N-methylbenz[indole-4,9- dione
  • Benz[f]indole-4,9-dione
  • Extracellular matrix
  • Matrix metalloproteinase
  • Membrane type 1-matrix metalloproteinase
  • Tissue inhibitor of metalloproteinase

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