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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.
Eur J Pharmacol. 2005 Dec 19; 527(1-3):31-6.EJ

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.

Authors+Show Affiliations

College of Pharmacy, Ewha Womans University, 11-1 Daehyun-Dong, Seodaemun-Ku, Seoul 120-750, Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16309669

Citation

Park, Hyen Joo, et al. "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." European Journal of Pharmacology, vol. 527, no. 1-3, 2005, pp. 31-6.
Park HJ, Lee HJ, Min HY, et al. 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. Eur J Pharmacol. 2005;527(1-3):31-6.
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. (2005). 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. European Journal of Pharmacology, 527(1-3), 31-6.
Park HJ, et al. 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. Eur J Pharmacol. 2005 Dec 19;527(1-3):31-6. PubMed PMID: 16309669.
* Article titles in AMA citation format should be in sentence-case
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, Y1 - 2005/11/23/ PY - 2005/06/27/received PY - 2005/09/27/revised PY - 2005/10/07/accepted PY - 2005/11/29/pubmed PY - 2006/2/9/medline PY - 2005/11/29/entrez SP - 31 EP - 6 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 527 IS - 1-3 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. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/16309669/Inhibitory_effects_of_a_benz[f]indole_49_dione_analog_on_cancer_cell_metastasis_mediated_by_the_down_regulation_of_matrix_metalloproteinase_expression_in_human_HT1080_fibrosarcoma_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(05)01067-8 DB - PRIME DP - Unbound Medicine ER -