title: Evaluation of melanogenesis in A-375 melanoma cells treated with 5,7-dimethoxycoumarin and valproic acid.
abstract: Malignant melanoma (melanoma malignum) is one of the most dangerous types of tumor. It is very difficult to cure. In recent years, a lot of attention has been given to chemoprevention. This method uses natural and synthetic compounds to interfere with and inhibit the process of carcinogenesis. In this study, a new treatment strategy was proposed consisting of a combination of 5,7-dimethoxycoumarin (DMC), an activator of melanogenesis, and valproic acid (VPA), a well-known drug that is one of the histone deacetylase inhibitors (HDACis). In conjunction with 1 mM VPA, all of the tested concentrations of DMC (10-150 μM) significantly decreased the proliferation of A-375 cells. VPA and DMC also induced the synthesis of melanin and the formation of dendrite and star-shaped cells. Tyrosinase gene expression and tyrosinase activity significantly increased in response to VPA treatment. Pyrolysis with gas chromatography and mass spectrometry (Py-GC/MS) was used to investigate the structure of the isolated melanin. This showed that the quantitative and qualitative components of melanin degradation products are dependent on the type of applied melanogenesis inductor. Products derived from eumelanin were detected in the pyrolytic profile of melanin isolated from A-375 cells stimulated with DMC. Thermal degradation of melanin isolated from melanoma cells after exposure to VPA or a mixture of VPA and DMC revealed the additional presence of products derived from pheomelanin.
authors.affiliation: Department of Biopharmacy, Medical University of Silesia, Sosnowiec, Poland. echodurek@sum.edu.pl
authors.forename: Ewa
authors.initials: E
authors.lastname: Chodurek
authors.forename: Arkadiusz
authors.initials: A
authors.lastname: Orchel
authors.forename: Joanna
authors.initials: J
authors.lastname: Orchel
authors.forename: Sławomir
authors.initials: S
authors.lastname: Kurkiewicz
authors.forename: Natalia
authors.initials: N
authors.lastname: Gawlik
authors.forename: Zofia
authors.initials: Z
authors.lastname: Dzierżewicz
authors.forename: Krystyna
authors.initials: K
authors.lastname: Stępień
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003374:Coumarins / Q000494:pharmacology*; D008401:Gas Chromatography-Mass Spectrometry; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D008543:Melanins / Q000378:metabolism; D008545:Melanoma / Q000378:metabolism / Q000473:pathology; D014442:Monophenol Monooxygenase / Q000235:genetics / Q000378:metabolism; D014635:Valproic Acid / Q000494:pharmacology*
chemical_list: D003374:Coumarins; D056572:Histone Deacetylase Inhibitors; D008543:Melanins; D014635:Valproic Acid; D014442:Monophenol Monooxygenase; C037446:5,7-dimethoxycoumarin