tolcapone and Melanoma

Catechol-O-methyltransferase (COMT) is a ubiquitous enzyme inactivating catecholic compounds. COMT is expressed also in human skin samples, and in melanoma cells it may be cytoprotective. A role of COMT in keratinocytes (HaCat) is unknown.. The objective of this study is: to investigate whether ultraviolet-B (UVB) radiation modifies COMT activity in melanocytes and HaCat and whether COMT inhibition plays a role in UVB-induced cell death.. Human cell lines of melanotic melanoma (SK-mel-1) and HaCat were used. COMT activity was evaluated under basal conditions and after UVB irradiation (311 nm) at a low (8 mJ/cm(2)) and a high dose (60 mJ/cm(2)). Tolcapone 1 μM was used to inhibit COMT.. Both SK-mel-1 and Ha-Cat cells express COMT activity. In SK-mel-1, COMT activity is reduced nearly 50% both 24 h and 48 h after a high dose UVB. In Ha-Cat cells, COMT activity increased 24 h after a high dose UVB but decreased at 48 h. Tolcapone increases significantly the cytotoxic effect of high dose UVB irradiation only in HaCat. High concentrations of tolcapone reduced melanin levels in melanoma cells parallel to reduced cell numbers.. Ultraviolet radiation differentially modifies COMT activity in melanoma cells and HaCat. Furthermore, tolcapone increased death of HaCat after irradiation but did not affect melanoma cells.

Topics: Benzophenones; Catechol O-Methyltransferase; Catechol O-Methyltransferase Inhibitors; Cell Death; Cell Line, Tumor; Enzyme Inhibitors; Humans; Keratinocytes; Melanoma; Neoplasm Proteins; Nitrophenols; Tolcapone; Ultraviolet Rays