title: Cell cycle arrest and differentiation induction by 5,7-dimethoxycoumarin in melanoma cell lines.
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.
authors.affiliation: Department of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica, 1-00133 Rome, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Alesiani
authors.forename: Rosella
authors.initials: R
authors.lastname: Cicconi
authors.forename: Maurizio
authors.initials: M
authors.lastname: Mattei
authors.forename: Carla
authors.initials: C
authors.lastname: Montesano
authors.forename: Roberto
authors.initials: R
authors.lastname: Bei
authors.forename: Antonella
authors.initials: A
authors.lastname: Canini
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002453:Cell Cycle; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D003374:Coumarins / Q000494:pharmacology*; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020128:Inhibitory Concentration 50; D008545:Melanoma / Q000188:drug therapy* / Q000378:metabolism*; D008546:Melanoma, Experimental / Q000188:drug therapy; D051379:Mice; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D014343:Trypan Blue / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D003374:Coumarins; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue; D014343:Trypan Blue; C037446:5,7-dimethoxycoumarin