Evaluation of melanogenesis in A-375 melanoma cells treated with 5,7-dimethoxycoumarin and valproic acid

Cellular & Molecular Biology Letters

Natalia Gawlik¹  Zofia Dzierżewicz⁴  Ewa Chodurek⁴  Joanna Orchel³  Krystyna Stępień²  Arkadiusz Orchel⁴  Sławomir Kurkiewicz² 

[1] Department of Biotechnology and Genetic Engineering, Medical University of Silesia, Sosnowiec, Poland$$;Department of Instrumental Analysis, Medical University of Silesia, Sosnowiec, Poland$$;Department of Molecular Biology, Medical University of Silesia, Sosnowiec, Poland$$;Department of Biopharmacy, Medical University of Silesia, Sosnowiec, Poland$$

关键词: A-375 cell line;    Malignant melanoma;    Valproic acid;    Tyrosinase;    Gene expression;    5;    7-dimethoxycoumarin;    Melanin;    Pyrolysis-gas chromatography/mass spectrometry;   

DOI  :  10.2478/s11658-012-0033-4

学科分类：分子生物学，细胞生物学和基因

来源: Uniwersytet Wroclawski * Wydzial Biotechnologii / University of Wroclaw, Faculty of Biotechnology

【 摘 要 】

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.

【 授权许可】

Unknown