In the present study we investigated the antiproliferative activity of 5,7-dimethoxycoumarin on the murine B16 and human A375 melanoma cell lines. The inhibitory concentration 50 (IC50) was estimated for each cell line by preliminary assay of tetrazolium salt reduction (MTT). With Trypan blue exclusion test we detected a cytostatic but not cytotoxic effect of the treatment in melanoma cells: 5,7-dimethoxycoumarin significantly reduced cell proliferation in a time- and dose-dependent manner, blocking the cell cycle in the G0/G1 phase both in B16 and A375 cells. Melanoma growth reduction was coupled to a differentiation process detected by monitoring some specific markers: i) morphological changes with development of dendrite-like projections from the cell surface; ii) melanin synthesis; and iii) PpIX accumulation. Induction of the differentiation process was more significant in murine melanoma cells, where the treatment irreversibly reduced cell growth. Consistent with G0/G1 arrest and melanogenesis in B16 cells, 5,7-dimethoxycoumarin strongly decreased activation of the mitogen-activated protein kinase extracellular signal-related kinase 1/2, which is upregulated in many types of cancer. These findings suggest that 5,7-dimethoxycoumarin should be further investigated through studies both in vitro, to identify the binding partners for this compound, and in preclinical animal models.

Alesiani, D., Cicconi, R., Mattei, M., Montesano, C., Bei, R., Canini, A. (2008). Cell cycle arrest and differentiation induction by 5,7-dimethoxycoumarin in melanoma cell lines. INTERNATIONAL JOURNAL OF ONCOLOGY, 32(2), 425-434.

Cell cycle arrest and differentiation induction by 5,7-dimethoxycoumarin in melanoma cell lines

ALESIANI, DANIELA;CICCONI, ROSELLA;MATTEI, MAURIZIO;MONTESANO, CARLA;BEI, ROBERTO;CANINI, ANTONELLA
2008

Abstract

In the present study we investigated the antiproliferative activity of 5,7-dimethoxycoumarin on the murine B16 and human A375 melanoma cell lines. The inhibitory concentration 50 (IC50) was estimated for each cell line by preliminary assay of tetrazolium salt reduction (MTT). With Trypan blue exclusion test we detected a cytostatic but not cytotoxic effect of the treatment in melanoma cells: 5,7-dimethoxycoumarin significantly reduced cell proliferation in a time- and dose-dependent manner, blocking the cell cycle in the G0/G1 phase both in B16 and A375 cells. Melanoma growth reduction was coupled to a differentiation process detected by monitoring some specific markers: i) morphological changes with development of dendrite-like projections from the cell surface; ii) melanin synthesis; and iii) PpIX accumulation. Induction of the differentiation process was more significant in murine melanoma cells, where the treatment irreversibly reduced cell growth. Consistent with G0/G1 arrest and melanogenesis in B16 cells, 5,7-dimethoxycoumarin strongly decreased activation of the mitogen-activated protein kinase extracellular signal-related kinase 1/2, which is upregulated in many types of cancer. These findings suggest that 5,7-dimethoxycoumarin should be further investigated through studies both in vitro, to identify the binding partners for this compound, and in preclinical animal models.
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/04 - Patologia Generale
English
Con Impact Factor ISI
Thiazoles; Gene Expression Regulation, Neoplastic; Animals; Melanoma, Experimental; Coumarins; Humans; Cell Line, Tumor; Inhibitory Concentration 50; Melanoma; Antineoplastic Agents; Disease Progression; Cell Differentiation; Mice; Trypan Blue; Tetrazolium Salts; Cell Cycle
Alesiani, D., Cicconi, R., Mattei, M., Montesano, C., Bei, R., Canini, A. (2008). Cell cycle arrest and differentiation induction by 5,7-dimethoxycoumarin in melanoma cell lines. INTERNATIONAL JOURNAL OF ONCOLOGY, 32(2), 425-434.
Alesiani, D; Cicconi, R; Mattei, M; Montesano, C; Bei, R; Canini, A
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/17535
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