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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
김춘미박혜영김화정이상국서은경
SCOPUS Author ID
김춘미scopus; 박혜영scopus; 김화정scopus; 서은경scopus
Issue Date
2005
Journal Title
European Journal of Pharmacology
ISSN
0014-2999JCR Link
Citation
European Journal of Pharmacology vol. 527, no. 41277, pp. 31 - 36
Indexed
SCI; SCIE; SCOPUS WOS 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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