Inhibition of Mek 1/2 kinase activity and stimulation of melanogenesis by 5,7-dimethoxycoumarin treatment of melanoma cells

  • Authors:
    • Daniela Alesiani
    • Rosella Cicconi
    • Maurizio Mattei
    • Roberto Bei
    • Antonella Canini
  • View Affiliations

  • Published online on: June 1, 2009     https://doi.org/10.3892/ijo_00000303
  • Pages: 1727-1735
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Abstract

In this study, the processes of differentiation and melanogenesis induced by 5,7-dimethoxycoumarin in murine (B16) and human (A375) melanoma cells were investigated. Taking into account the previously demonstrated antiproliferative and differentiation activities of this compound, we examined Ras/Raf/Mek/Erk mitogen-activated protein kinase activity following treatment; inhibition of Mek 1/2 kinase activity and subsequent reduction in Erk 1/2 activation were detected in both cell types. We observed melanogenesis induction associated to an increase in cAMP-response element-binding protein (CREB) and microphthalmia-associated transcription factor (Mitf) expression, both involved in its regulation. Mitf is fundamental for development, survival and differentiation of melanocyte and melanoma, since it regulates transcription of genes encoding for proteins involved in cell cycle progression or in melanogenesis, such as the enzyme tyrosinase. A significant increase of tyrosinase activity was revealed following treatment in B16 but not in A375 cells, although a strong synthesis of melanin was induced by 5,7-dimethoxycoumarin in both cell lines. The treatment induced protoporphyrine IX accumulation involved in melanogenesis since it promotes stability of cAMP. Finally, the Mek 1/2 inhibitor U0126 significantly potentiated growth inhibition of B16 cells triggered by 5,7-dimethoxycoumarin, suggesting that down-regulation of Raf/Mek/Erk pathway sensitizes melanoma cells to 5,7-dimethoxycoumarin treatment.

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June 2009
Volume 34 Issue 6

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

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Spandidos Publications style
Alesiani D, Cicconi R, Mattei M, Bei R and Canini A: Inhibition of Mek 1/2 kinase activity and stimulation of melanogenesis by 5,7-dimethoxycoumarin treatment of melanoma cells. Int J Oncol 34: 1727-1735, 2009.
APA
Alesiani, D., Cicconi, R., Mattei, M., Bei, R., & Canini, A. (2009). Inhibition of Mek 1/2 kinase activity and stimulation of melanogenesis by 5,7-dimethoxycoumarin treatment of melanoma cells. International Journal of Oncology, 34, 1727-1735. https://doi.org/10.3892/ijo_00000303
MLA
Alesiani, D., Cicconi, R., Mattei, M., Bei, R., Canini, A."Inhibition of Mek 1/2 kinase activity and stimulation of melanogenesis by 5,7-dimethoxycoumarin treatment of melanoma cells". International Journal of Oncology 34.6 (2009): 1727-1735.
Chicago
Alesiani, D., Cicconi, R., Mattei, M., Bei, R., Canini, A."Inhibition of Mek 1/2 kinase activity and stimulation of melanogenesis by 5,7-dimethoxycoumarin treatment of melanoma cells". International Journal of Oncology 34, no. 6 (2009): 1727-1735. https://doi.org/10.3892/ijo_00000303