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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Disulfiram Suppresses Invasive Ability of Osteosarcoma Cells Via the Inhibition of MMP-2 and MMP-9 Expression

  • Cho, Hyun-Ji (Research Institute of Biomedical Engineering, Catholic University of Daegu School of Medicine) ;
  • Lee, Tae-Sung (Research Institute of Biomedical Engineering, Catholic University of Daegu School of Medicine) ;
  • Park, Jae-Bok (Department of Medicine, Catholic University of Daegu School of Medicine) ;
  • Park, Kwan-Kyu (Research Institute of Biomedical Engineering, Catholic University of Daegu School of Medicine) ;
  • Choe, Jung-Yoon (Research Institute of Biomedical Engineering, Catholic University of Daegu School of Medicine) ;
  • Sin, Doo-Il (Department of Medicine, Catholic University of Daegu School of Medicine) ;
  • Park, Yoon-Yub (Research Institute of Biomedical Engineering, Catholic University of Daegu School of Medicine) ;
  • Moon, Yong-Suk (Research Institute of Biomedical Engineering, Catholic University of Daegu School of Medicine) ;
  • Lee, Kwang-Gill (Department of Agricultural Biology, National Institute of Agricultural Science and Technology) ;
  • Yeo, Joo-Hong (Department of Agricultural Biology, National Institute of Agricultural Science and Technology) ;
  • Han, Sang-Mi (Department of Agricultural Biology, National Institute of Agricultural Science and Technology) ;
  • Cho, Young-Su (Division of Biotechnology, Faculty of Natural Resources and Life Science, Dong-A University) ;
  • Choi, Myeong-Rak (Department of Biotechnology, Chonnam National University) ;
  • Park, Nam-Gyu (Department of Biotechnology and Bioengineering, Pukyong National University) ;
  • Lee, Yun-Sik (Department of Medical Zoology, College of Medicine, Kyung Hee University) ;
  • Chang, Young-Chae (Research Institute of Biomedical Engineering, Catholic University of Daegu School of Medicine)
  • Published : 2007.11.30
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Abstract

Cancer cells, characterized by local invasion and distant metastasis, are very much dependant on the extracellular matrix. The expression of matrix metalloproteinases (MMPs) has been implicated in the invasion and metastasis of cancer cells. In this study, we reported the effects of disulfiram, a clinically used anti-alcoholism drug, on tumor invasion suppression, as well as its effects on the activity of MMP-2 and MMP-9 in human osteosarcoma cells (U2OS). Disulfiram has been used for alcohol aversion therapy. However, recent reports have shown that disulfiram may have potential in the treatment of human cancers. Herewith, we showed that the anti-tumor effects of disulfiram, in an invasion assay using U2OS cells and that disulfiram has a type IV collagenase inhibitory activity that inhibits expression of genes and proteins responsible for both cell and non-cell mediated invasion on pathways. In conclusion, disulfiram inhibited expression of MMP-2 and MMP-9 and it regulated the invasion of human osteosarcoma cells. These observations raise the possibility of disulfiram being used clinical for the inhibition of cancer invasion.

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References

  1. Brar, S. S., Grigg, C., Wilson, K. S., Holder, W. D., Jr., Dreau, D., Austin, C., Foster, M., Ghio, A. J., Whorton, A. R., Stowell, G. W., Whittall, L. B., Whittle, R. R., White, D. P. and Kennedy, T. P. (2004) Disulfiram inhibits activating transcription factor/cyclic AMP-responsive element binding protein and human melanoma growth in a metal-dependent manner in vitro, in mice and in a patient with metastatic disease. Mol. Cancer Ther. 3, 1049-1060.
  2. Chen. D., Cui, I. C., Yang, H. and Dou, Q. P. (2006) disulfiram, a clinically used anti-alcoholism drug and copper-binding agent, induces apoptotic cell death in breast cancer cultures and zenografts via inhibition of the proteasome activity. Cancer Res. 66, 10425-10433. https://doi.org/10.1158/0008-5472.CAN-06-2126
  3. Cho, J. J., Kang, J. H., Kwak, J. Y., Lee, T. S., Lee, I. S., Park, N. G., Hiroo, N., Jinji, M. and Chang, Y. C. (2007) Ascofuranone suppresses PMA-mediated matrix metalloproteinase-9 gene activation through the Ras/Raf/MEK/ERK-and Ap1-dependent mechanisms. Carcinogenesis 28, 1101-1110.
  4. Christofori, G. (2006) New signals from the invasive front. Nature 441, 444-450. https://doi.org/10.1038/nature04872
  5. Dhawan, M., Flora, S. J., Singh, S. and Tandon, S. K. (1989) Chelation of lead during co-exposure to ethanol. Biochem. Int. 19, 1067-1075.
  6. Hong, S., Park, K. K., Magae, J., Ando, K., Lee, T. S., Kwon, T. K., Kwak, J. Y., Kim, C. H. and Chang, Y. C. (2005) Ascochlorin inhibits matrix metalloproteinase-9 expression by suppressing activator protein-1-mediated gene expression through the ERK1/2 signaling pathway: inhibitory effects of ascochlorin on the invasion of renal carcinoma cells. J. Biol. Chem. 280, 25202-25209. https://doi.org/10.1074/jbc.M413985200
  7. Huang, S. C., Ho, C. T., Lin-Shiau, S. Y. and Lin, J. K. (2005) Carnosol inhibits the invasion of B16/F10 mouse melanoma cells by suppressing metalloproteinase-9 through down-regulating nuclear factor-kappa B and c-Jun. Biochem. Pharmacol. 69, 221-232. https://doi.org/10.1016/j.bcp.2004.09.019
  8. Lee, P. P., Hwang, J. J., Murphy, G. and Ip, M. M. (2005) Functional significance of MMP-9 in tumor necrosis factor-induced proliferation and branchig morphogenesis of mammary epithelial cells. Endocrinology 141, 3764-3773. https://doi.org/10.1210/en.141.10.3764
  9. Li, L., Abe, Y., Kanagawa, K., Shoji, T., Mashino, T., Mochizuki, M., Tanaka, M. and Miyata, N. (2007) Iron-chelating agents never suppress fenton reaction but participate in quenching spin-trapped radicals. Anal. Chim. Acta 599, 315-319. https://doi.org/10.1016/j.aca.2007.08.008
  10. Liotta, L. A., Steeg, P. S. and Stetler-Stevenson, W. G. (1991) Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation. Cell 64, 327-326. https://doi.org/10.1016/0092-8674(91)90642-C
  11. Lipsky, J. J., Shen, M. L. and Naylor, S. (2001) In vivo inhibition of aldehyde dehydrogenase by disulfiram. Chem. Biol. Interact. 130, 93-102. https://doi.org/10.1016/S0009-2797(00)00225-8
  12. Liu, G. Y., Frank, N., Bartsch, H. and Lin, J. K. (1998) Induction of apoptosis by thiuramdisulfides, the reactive metabolites of dithiocarbamates, through coordinative modulation of NFkappaB, c-fos/c-jun, and p53 proteins. Mol. Carcinog. 22, 235-246. https://doi.org/10.1002/(SICI)1098-2744(199808)22:4<235::AID-MC5>3.0.CO;2-I
  13. Ma, Z., Chang, M. J., Shah, R., Adamski, J., Zhao, X. and Benveniste, E. N. (2004) Brg-1 is required for maximal transcription of the human matrix metalloproteinase-2 gene. J. Biol. Chem. 279, 46326-46334. https://doi.org/10.1074/jbc.M405438200
  14. Marikovsky, M., Ziv, V., Nevo, N., Harris-Cerruti, C. and Mahler, O. (2003) Cu/Zn superoxide dismutase plays important role in immune response. J. Immunol. 170, 2993-3001. https://doi.org/10.4049/jimmunol.170.6.2993
  15. Masahiro, I., Akira, N., Takashi F., Noriyuki, A., Kengo, M., Toshiaki, E., Koichi, Y., Ryuji, M., Takayuki, Y. and Ryuichi, K. (2002) Anti-invasive effect of MMI-166, a new selective matrix metalloproteinase inhibitor, in Cervical Carcinoma Cell lines. Gynechol. Oncol. 85, 103-107. https://doi.org/10.1006/gyno.2001.6573
  16. Matsunaga, Y., Koda, M. and Murawaki, Y. (2004) Expression of matrix metalloproiteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in hepatocellular carcinoma tissue, compared with the surrounding non-tumor tissue. Res. Commun. Mol. Pathol. Pharmacol. 115, 143-150.
  17. McDonnel, N. B., De Guznman, R. R., Rice, W. G., Turpin, J. A. and Summers, M. F. (1997) Zine ejection as a new rationale for the use of cystamine and related sidulfide-containing antiviral agents in the treatment of AIDS. J. Med. Chem. 40, 1969-1976. https://doi.org/10.1021/jm970147+
  18. Nash, T. and Rice, W. G. (1998) Efficacies of zine-finger-active drugs against giardialamblia. Antimicrob. Agents Chemother. 42, 1488-1492.
  19. Qin, H., Sun, Y. and Benveniste, E. N. (1999) The transcription factors Sp1, Sp3, and AP-2 are required for constitutive matrix metalloproteinase-2 gene expression in astroglioma cells. J. Biol. Chem. 274, 29130-29137. https://doi.org/10.1074/jbc.274.41.29130
  20. Sato, H. and Seiki, M. (1993) Regulatory mechanism of 92 kDa type IV collagenase gene expression which is associated with invasiveness of tumor cells. Oncogene 8, 395-405.
  21. Sauna, Z. E., Shukla, S. and Ambudkar, S. V. (2005) Disulfiram, an old drug with new potential therapeutic uses for human cancers and fungal infections. Mol. Biosyst. 1, 127-134. https://doi.org/10.1039/b504392a
  22. Shen, M. J., Lipsky, J. J. and Naylor, S. (2000) Role of Disulfiram in the In Vitro Inhibition of Rat Liver Mitochondrial Aldehyde Dehydrogenase. Biochem. Pharmacol. 60, 947-953. https://doi.org/10.1016/S0006-2952(00)00435-4
  23. Shian, S. G., Kao, Y. R., Wu, F. Y. and Wu, C. W. (2003) Inhibition of invasion and angiogenesis by zinc-chelating agent disulfiram. Mol. Pharmacol. 64, 1076-1084. https://doi.org/10.1124/mol.64.5.1076
  24. Soini, Y., Satta, J., Maatta, M. and Autio-Harmainen, H. (2001) Expression of MMP2, MMP9, MT1-MMP, TIMP1, and TIMP2 mRNA in valvular lesions of the heart. J. Pathol. 194, 225-231. https://doi.org/10.1002/path.850
  25. Soreide, K., Janssen, E. A., Korner, H. and Baak, J. P. (2006) Trypsin in colorectal cancer: molecular biological mechanisms of proliferation, invasion, and metastasis. J. Pathol. 209, 147-156. https://doi.org/10.1002/path.1999
  26. Stetler-Stevenson, W. G., Brown, P. D., Onisto, M., Levy, A. T. and Liotta, L.A. (1990) Tissue inhibitor of metalloproteinases-2 (TIMP-2) mRNA expression in tumor cell lines and human tumor tissues. J. Biol. Chem. 265, 13933-13938.
  27. Stewart, D. A., Cooper, C. R. and Sikes, R. A. (2004) Changes in extracellular matrix (ECM) and ECM-associated proteins in the metastatic progression of prostate cancer. Reprod. Biol. Endocrinol. 2, 2. https://doi.org/10.1186/1477-7827-2-2
  28. Tanimura, S., Kadomoto, R., Tanaka, T., Zhang, Y. J., Kouno, I. and Kohno, M. (2005) Suppression of tumor cell invasiveness by hydrolyzable tannins (plant polyphenols) via the inhibition of matrix metalloproteinase-2/-9 activity. Biochem. Biophys. Res. Commun. 330, 1306-1313. https://doi.org/10.1016/j.bbrc.2005.03.116
  29. Woo, J. H., Lim, J. H., Kim, Y. H., Suh, S. I., Min, D. S., Chang, J. S., Lee, Y. H., Park, J. W. and Kwon, T. K. (2004) Resveratrol inhibits phorbol myristate acetate-induced matrix metalloproteinase-9 expression by inhibiting JNK and PKC delta signal transduction. Oncogene 23, 1845-1853. https://doi.org/10.1038/sj.onc.1207307
  30. Yao, J., Xiong, S., Klos, K., Nguyen, N., Grijalva, R., Li, P. and Yu, D. (2001) Multiple signaling pathways involved in activation of matrix metalloproteinase-9 (MMP-9) by heregulin-beta1 in human breast cancer cells. Oncogene 20, 8066-8074. https://doi.org/10.1038/sj.onc.1204944
  31. Yasuhito, K., Ysuyoshi, Y. and Mutsuo, I. (2002) Relationship between expression of matrix metalloproteinase-2 and matrix metalloproteinase-9 and invasion ability of cervical cancer cells. Oncol. Rep. 9, 565-569.
  32. Yoon, S. O., Kim, M. M. and Chung, A. S. (2001) Inhibitory effect of selenite on invasion of HT1080 tumor cells. J. Biol. Chem. 276, 20085-20092. https://doi.org/10.1074/jbc.M101143200

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