Inhibition of calcineurin by cyclosporine A exerts multiple effects on human melanoma cell lines HT168 and WM35

  • Authors:
    • Tamás Juhász
    • Csaba Matta
    • Gábor Veress
    • Georgina Nagy
    • Zsolt Szíjgyártó
    • Zsanett Molnár
    • János Fodor
    • Róza Zákány
    • Pál Gergely
  • View Affiliations

  • Published online on: April 1, 2009     https://doi.org/10.3892/ijo_00000225
  • Pages: 995-1003
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Abstract

The immunosuppressant cyclosporine A (CsA) is a specific pharmacological inhibitor of calcineurin, the Ca2+-calmodulin activated phospho-Ser/Thr-specific protein phosphatase. Although calcineurin-inhibiting compounds are applied for local treatment of psoriasis or atopic dermatitis in dermatological practice, little is known about the functions of calcineurin in epidermis-derived malignancies. We investigated the effects of CsA on two human melanoma cell lines, the metastasis forming HT168 and WM35 established from an RGP primary lesion. CsA of 2 µM lowered the enzyme activity by 50% and caused elevation in both mRNA and protein expression of calcineurin. Cell proliferation was diminished, as well as the cellular morphology and the actin organization were altered in both cell lines. CsA increased cell death moderately in both cell lines and reduced the metabolic activity of HT168 cells, but not that of WM35 cells. CsA also elevated the expressions of both Bcl-2 and ERK1/2. Fibronectin guided migration of HT168 cells was stimulated under the effect of CsA, while that of WM35 cells was reduced, moreover, HT168 cells switched from the expression of β3 to β1 integrin, but WM35 cells continued to express β3. Based on our results we propose a multiple, partly malignancy-dependent role of calcineurin in these melanoma cell lines.

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April 2009
Volume 34 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Juhász, T., Matta, C., Veress, G., Nagy, G., Szíjgyártó, Z., Molnár, Z. ... Gergely, P. (2009). Inhibition of calcineurin by cyclosporine A exerts multiple effects on human melanoma cell lines HT168 and WM35. International Journal of Oncology, 34, 995-1003. https://doi.org/10.3892/ijo_00000225
MLA
Juhász, T., Matta, C., Veress, G., Nagy, G., Szíjgyártó, Z., Molnár, Z., Fodor, J., Zákány, R., Gergely, P."Inhibition of calcineurin by cyclosporine A exerts multiple effects on human melanoma cell lines HT168 and WM35". International Journal of Oncology 34.4 (2009): 995-1003.
Chicago
Juhász, T., Matta, C., Veress, G., Nagy, G., Szíjgyártó, Z., Molnár, Z., Fodor, J., Zákány, R., Gergely, P."Inhibition of calcineurin by cyclosporine A exerts multiple effects on human melanoma cell lines HT168 and WM35". International Journal of Oncology 34, no. 4 (2009): 995-1003. https://doi.org/10.3892/ijo_00000225