Skip to main content
Log in

Proteomic analysis and the antimetastatic effect ofN-(4-methyl)phenyl-O-(4-methoxy) phenyl-thionocarbamate-induced apoptosis in human melanoma SK-MEL-28 cells

  • Articles
  • Drug Development
  • Published:
Archives of Pharmacal Research Aims and scope Submit manuscript

Abstract

We employed human SK-MEL-28 cells as a model system to identify cellular proteins that accompanyN-(4-methyl)phenyl-O-(4-methoxy)phenyl-thionocarbamate (MMTC)-induced apoptosis based on a proteomic approach. Cell viability tests revealed that SK-MEL-28 skin cancer cells underwent more cell death than normal HaCaT cells in, a dose-dependent manner after treatment with MMTC. Two-dimensional electrophoresis in conjunction with matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry analysis or computer matching with a protein database further revealed that the MMTC-induced apoptosis is accompanied by increased levels of caspase-1, checkpoint suppressor-1, caspase-4, NF-κB inhibitor, AP-2, c-Jun-N-terminal kinase, melanoma inhibitor, granzyme K, G1/S specific cyclin D3, cystein rich protein, Ras-related protein Rab-37 or Ras-related protein Rab-13, and reduced levels of EMS (oncogene), ATP synthase, tyrosine-phosphatase, Cdc25c, 14-3-3 protein or specific structure of nuclear receptor. The migration suppressing effect of MMTC on SK-MEL-28 cell was tested. MMTC suppressed the metastasis of SK-MEL-8 cells. It was also identified that MMTC had little angiogenic effect because it did not suppress the proliferation of HUVEC cell line. These results suggest that MMTC is a novel chemotherapeutic and metastatic agents against the SK-MEL-28 human melanoma cell line.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Ashkenazi, A., Death receptor: Signaling and modulation.Science, 281, 1322–1326 (1998).

    Article  Google Scholar 

  • Berke, G., The CTL's kiss of death,Cell, 81, 9–12 (1995).

    Article  PubMed  CAS  Google Scholar 

  • Berke, G., Unlocking the secrets of CTL and NK cells.Immunol. Today., 16, 343–346 (1995).

    Article  PubMed  CAS  Google Scholar 

  • Boldin, M. P., Goncharov, T. M., Goltsev, Y. V., and Wallach, D., Involvement of MACH, a novel MORT1/FADD interacting protease, in Fas/APO-1 and TNFReceptor-induced cell death.Cell, 85, 803–815 (1996).

    Article  PubMed  CAS  Google Scholar 

  • Casano, F. J., Rolando, A. M., Mudgett, J. S., and Molineaux, S. M., The structure and complete nucleotide sequence of the murine gene encoding interlekin-1β converting enzyme (ICE).Genomics, 20, 474–481 (1994).

    Article  PubMed  CAS  Google Scholar 

  • Cen, D., Gonzalez, R. I., Buckmeier, J. A., Kahlon, R. S., Tohidian, N. B., and Meyskens, F. L., Jr., Disulfiram induces apoptosis human melanoma cell via redox-related process,Mol. Cancer Ther., 1, 197–204 (2002).

    PubMed  CAS  Google Scholar 

  • Chen, C. Y. and Faller, D. V., Direction of p21 ras-generated signals towards cell growth or apoptosis is determined by protein kinase C and Bcl-2.Oncogene, 11, 1487–1698 (1995).

    PubMed  CAS  Google Scholar 

  • Chinnaiyan, A. M., O'Rourke, K., Tewari, M., and Dixit, V. M., FADD, a novel death domain-containing protein, interacts with the death domain of Das and initiates apoptosis.Cell, 81, 505–512 (1995).

    Article  PubMed  CAS  Google Scholar 

  • Elledge, S. J., Cell cycle checkpoints: Preventing an identity crisis.Science, 274, 1664–1667 (1996).

    Article  PubMed  CAS  Google Scholar 

  • Estus, S., Zaks, W. J., Freeman, R. S., Gruda, M., Bravo, R., and Johnson, E. M., Altered gene expression in neurons during programmed cell death: identification of c-JUN as necessary for neuronal apoptosis.J. Cell Biol., 127, 1717–1727 (1994).

    Article  PubMed  CAS  Google Scholar 

  • Fidler, I. J., Schackert, G., Zhang, R. D., Radinsky, R., and Fujimaki, T.,Cancer and Metastasis Reviews, 18, 387–400 (1999).

    Article  PubMed  CAS  Google Scholar 

  • Folkman, J. and Shing, Y., Angiogenesis.J. Biol. Chem., 267, 10931–10934 (1992).

    PubMed  CAS  Google Scholar 

  • Ham, J., Babij, C., Whitfield, J., Pfarrc, M., Lallemand, D., Yamiv, M., and Rubin, L., A c-Jun dominant negative mutant protects sympathetic neurons against programmed cell death.Neuron, 14, 927–939 (1995).

    Article  PubMed  CAS  Google Scholar 

  • Hanabuchi, S., Koyanagi, M., Yonehara, S., Yagita, H., and Okumura, K., Fas and its ligand in a general mechanism of T-cell mediated cytotoxicity.Proc. Natl. Acad. Sci., USA., 91, 4930–4934 (1994).

    Article  PubMed  CAS  Google Scholar 

  • Hanahan, D. and Weinberg, R. A., The hall-mark of cancer,Cell, 100, 57–70 (2000).

    Article  PubMed  CAS  Google Scholar 

  • Henkart, P. A., Lymphocyte-mediated cytotoxicity: Two pathways and multiple effector.Immunity, 1, 343–346 (1994).

    Article  PubMed  CAS  Google Scholar 

  • Henkart, P. A., ICE-family proteases: Mediators of all apoptotic cell death?Immunity, 4, 195–201 (1996).

    Article  PubMed  CAS  Google Scholar 

  • Hofmann, K., Bucher, P., and Tschopp, J., The CARD domain: a new apoptotic signaling motif.Trends Biochem. Sci., 22, 155–156 (1997)

    Article  PubMed  CAS  Google Scholar 

  • Kamens, J., Paskind, M., Hugunin, M., Talanian, R. V., Allen, H., Banach, D., Bump, N., Hackett, M., Johnston, C. G., Li, P., Mankovich, J. A., Terranova, M., and Ghayur, T., Identification and characterization of ICH-2, a novel member of the interleukin-1β-converting enzyme family of cystein proteases.J. Biol. Chem., 270, 15250–15256 (1995).

    Article  PubMed  CAS  Google Scholar 

  • Kauffmann-Zeh, A., Rodriguez-Viciana, E., Ulrich, P., Gilbert, C., Coffer, P., Downward, J., and Evan, G., Suppression of c-Myc-induced apoptosis by Ras signaling through PI(3)K and PKB.Nature, 385, 544–548 (1997).

    Article  PubMed  CAS  Google Scholar 

  • Kaufmann, S. H., Desnoyers, S., Ottaviano, Y., Davidson, N. E., and Poirier, G. G., Specific proteolytic cleavage of poly (ADP-ribose) polymerase: an early marker of chemotherapy-induced apoptosis.Cancer Res., 53, 3976–3985 (1993).

    PubMed  CAS  Google Scholar 

  • Liu, G. Y., Frank, N., Bartsch, H., and Lin, J. K., Induction of apoptosis by thiuramdisulfides, the reactive metabolites of dithiocarbamates, through coordinative modulation of NF-kappa B,c-fos/c-jun, and p53 proteins.Mol. Carcinog., 22, 235–246 (1998).

    Article  PubMed  CAS  Google Scholar 

  • Menashe, B. E., Role of AP-2 in tumor growth and metastasis of human melanoma.Cancer and Metastasis Reviews, 18, 377–385 (1999).

    Article  Google Scholar 

  • Mesner, P. W., Epiting, C. L., Megarty, J. L., and Green, S. H., A time table of events during programmed cell death induced by trophic factor withdrawal from neuronal PC12 cells.J. Neurosci., 15, 7357–7366 (1995).

    PubMed  CAS  Google Scholar 

  • Moellering, D., McAndrew, J., Jo, Ho., and Darley-Usmar, V. M., Effect of pyrolidine dithiocarbamate on endothelial cells: Protection against oxidative stress.Free Radical Biol. Med., 26, 1138–1145 (1999).

    Article  CAS  Google Scholar 

  • Morton, D. L. and Barth, A., Vaccine therapy for malignant melanoma. CA.Cancer J. Clin., 46, 225–244 (1996).

    Article  PubMed  CAS  Google Scholar 

  • Muzio, M., Chinnaiyan, A. M., Kischkel, F. C., O'Rourke, K., Shevchenko, A., Ni, J., Scaffidi, C., Bretz, J. D., Zhang, M., Gentz, R., Mann, M., Krammer, K. H., Peter, M. E., and Dixit, V. M., FLICE, a novel FADD-Homologous ICE/CED-3 like protease is recruited to the CD95 (Fas/APO-1) death inducing-signaling complex.Cell, 85, 817–827 (1996).

    Article  PubMed  CAS  Google Scholar 

  • Qu, C. K., Role of the SHP-2-tyrosine phosphatase in cytokine-induced signaling and cellular response.Biochim. Biophys. Acta., 1592, 297–301 (2002).

    Article  PubMed  CAS  Google Scholar 

  • Rodriguez-Vicente, J., Vicente-Ortega, V., and Canteras-Jordana, M., Effects of different antineoplastic agents and a pretreatment by modulators n three melanoma lines.Cancer, 82, 495–502 (1988).

    Article  Google Scholar 

  • Rudolfo, M., Daniotti, M., and Vallacchi, V., Genetic progression of metastatic melanoma. Cancer Lett., 214, 133–147 (2004).

    Article  Google Scholar 

  • Satyamoorthy, K., Meler, F., Ksu, M. Y., Berking, C., and Herhyn, M., Human xenografts, human skin and skin reconstructs for studies in melanoma development and progression.Cancer and Metastasis Reviews, 18, 401–405 (1995).

    Article  Google Scholar 

  • Schadendorf, D., Worm, M., Algermissen, B., Kohlmus, C. M., and Czarnetzki, B. M., Chemosensitivity testing of human malignant melanoma. A retrospective analysis of clinical reponse and in vitro drug sensitivity.Cancer, 73, 103–108 (1994).

    Article  PubMed  CAS  Google Scholar 

  • Shi, L., Kam, C. M., Powers, J. C., Aebersold, R., and Greenberg, A. H., Purification of three cytotoxic lymphocyte granule serine proteases that inducd apoptosis through distinct substrate and target cell interactions.J. Exp. Med., 176, 1521–1529 (1992).

    Article  PubMed  CAS  Google Scholar 

  • Shi, L., Kraut, R. P., Aerersold, R., and Greenberg, A. H., A natural killer cell granule protein that induces DNA fragmentation and apoptosis.J. Exp. Med., 175, 553–566 (1992).

    Article  PubMed  CAS  Google Scholar 

  • Singh, A. K., Seth, P., Anthony, P., Husain, M. M., Madhavan, S., Mukhtar, H., and Maheshwari, R. K., Green tea constituent epigallocatechin-3-gallate inhibits angiogenic differentiation of human endothelial cells.Archives of Biochemistry and Biophysics, 401, 29–37 (2002).

    Article  PubMed  CAS  Google Scholar 

  • Smyth, M. J. and Trapani, J. A., Granzymes: exogenous porteinases that induce target cell apoptosis.Immunol. Today, 16, 202–206 (1995).

    Article  PubMed  CAS  Google Scholar 

  • Suda, T., Takahashi, T., Golstein, P., and Nagata, S., Molecular cloning and expression of the Fas ligand, a novel member of the Tumor Necrosis Factor family.Cell, 75, 1169–1178 (1993).

    Article  PubMed  CAS  Google Scholar 

  • Sung, N. D., Myung, P. K., Seong, M. G., Yu, S. J., and Choi, S. L., QSAR anlyses on the cell cytotoxicity of someN-phenyl-O-phenylthionocarbamate derivatives using Comparative Molecular Field Analysis (CoMFA) based on different alignment approaches and Holographic Quantitative Structure-Activity Relationship (QSAR),Agri. Chem. Biotechnol., 46, 137–143 (2003).

    CAS  Google Scholar 

  • Sung, N. D. and Soung, M. K., Phenyl substituents effect on the fungicidal activity ofN-phenyl-O-phenylthiono carbamate derivatives.Kor. J. Pestic. Sci., 3, 29–36 (1999).

    Google Scholar 

  • Takahashi, T., Tanaka, M., Brannan, C. I., Jenkins, N. A., Copeland, N. G., Suda, T., and Nagata, S., Generalized lymphoproliferative disease in mice, caused by a point mutation in the Fas ligand.Cell, 76, 969–976 (1994).

    Article  PubMed  CAS  Google Scholar 

  • Takakura, K., Sano, K., Hojo, S., and Hirano, A., Metastatic tumors of the central nervous system.Igaku- shoin Ltd. Tokyo, Japan, (1982).

    Google Scholar 

  • Tewari, M., Telford, W. G., Miller, R. A., and Dixit, V. M., Crm A, a poxvirus-encoded serpin, Inhibits cytotoxic T-lymphocyte-mediated apoptosis.J. Biol. Chem., 270, 22705–22708 (1995).

    Article  PubMed  CAS  Google Scholar 

  • Tom, J. and Dafna, B. S., Suppression of Ras-induced apoptosis by the RacGTPase.Mol. Cell Biol., 19, 5892–5901 (1999).

    Google Scholar 

  • Toru, T., Akio, S., and John, D. M., The prodomain of caspase-1 enhances Fas-mediated apoptosis through facilitation of caspase-8 activation.J. Biol. Chem., 275, 14248–14254 (2000).

    Article  Google Scholar 

  • Trede, N. S., Tsytsykova, A. V., Chatila, T., Goldfeld, A. E., and Geha, R. S., Transcriptional activation of the human TNF-alpha promoter by super antigen in human monocytic cells: role of NF-kappa B.J. Immunol., 155, 902–908 (1995).

    PubMed  CAS  Google Scholar 

  • Wheeler, M. A., Townsend, M. K., Yunker, L. A., and Mauro, L. J., Transcriptional activation of the tyrosine phosphatase gene, OST-PTP during osteoblast differentiation.J. Cell. Biochem., 87, 363–376 (2002).

    Article  PubMed  CAS  Google Scholar 

  • Wu, H. and Lozano, G., NF-kappa B activation of p53. A potential mechanism for suppressing cell growth in response to stress.J. Biol. Chem., 269, 20067–20074 (1994).

    PubMed  CAS  Google Scholar 

  • Xia, Z., Dickens, M., Rainge, J., Davis, R. J., and Greenberg, M. E., Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis.Science, 270, 1326–1331 (1995).

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Choi, SL., Choi, YS., Kim, YK. et al. Proteomic analysis and the antimetastatic effect ofN-(4-methyl)phenyl-O-(4-methoxy) phenyl-thionocarbamate-induced apoptosis in human melanoma SK-MEL-28 cells. Arch Pharm Res 29, 224–234 (2006). https://doi.org/10.1007/BF02969398

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02969398

Key words

Navigation