TY - JOUR
T1 - 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
AU - Park, Hyen Joo
AU - Lee, Hyun Jung
AU - Min, Hye Young
AU - Chung, Hwa Jin
AU - Suh, Myung Eun
AU - Park-Choo, Hye Young
AU - Kim, Choonmi
AU - Kim, Hwa Jung
AU - Seo, Eun Kyung
AU - Lee, Sang Kook
N1 - Funding Information:
This work was supported in part by a Korea Research Foundation Grant (KRF-2003-E00004).
PY - 2005/12/19
Y1 - 2005/12/19
N2 - 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.
AB - 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.
KW - 2-Amino-3-ethoxycarbonyl-N-methylbenz[indole-4,9- dione
KW - Benz[f]indole-4,9-dione
KW - Extracellular matrix
KW - Matrix metalloproteinase
KW - Membrane type 1-matrix metalloproteinase
KW - Tissue inhibitor of metalloproteinase
UR - http://www.scopus.com/inward/record.url?scp=28544436746&partnerID=8YFLogxK
U2 - 10.1016/j.ejphar.2005.10.009
DO - 10.1016/j.ejphar.2005.10.009
M3 - Article
C2 - 16309669
AN - SCOPUS:28544436746
SN - 0014-2999
VL - 527
SP - 31
EP - 36
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 1-3
ER -