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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
- Title
- 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
- Authors
- Park H.J.; Lee H.-J.; Min H.-Y.; Chung H.-J.; Suh M.E.; Park-Choo H.-Y.; Kim C.; Kim H.J.; Seo E.-K.; Lee S.K.
- Ewha Authors
- 김춘미; 박혜영; 김화정; 이상국; 서은경
- SCOPUS Author ID
- 김춘미; 박혜영; 김화정; 이상국; 서은경
- Issue Date
- 2005
- Journal Title
- European Journal of Pharmacology
- ISSN
- 0014-2999
- Citation
- European Journal of Pharmacology vol. 527, no. 41277, pp. 31 - 36
- Indexed
- SCI; SCIE; SCOPUS
- Document Type
- Article
- 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. © 2005 Elsevier B.V. All rights reserved.
- DOI
- 10.1016/j.ejphar.2005.10.009
- Appears in Collections:
- 약학대학 > 약학과 > Journal papers
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