CATECHOL-O-METHYLTRANSFERASE AS A TARGET FOR MELANOMA DESTRUCTION

Catechols may interfere in melanogenesis by causing increased levels o f toxic quinones. Several catechols and known inhibitors of the enzyme catechol-O-methyltransferase (COMT) were therefore tested for their t oxicity towards a pigmented melanoma cell line, UCLA-SO-(M14). The inh ibition of thymidine incorporation as a result of exposure to the comp ounds was measured. All agents were compared to 4-hydroxyanisole (4HA) , a depigmenting agent extensively studied as an antimelanoma drug. Th e compounds were also tested on the epithelial cell line, CNCM-I-(221) in the presence and absence of tyrosinase. All the compounds were mor e effective than 4HA towards the M14-cells at either 10(-4) M or 10(-5 ) M. The toxicity of 4HA towards the 221-cells was shown to be complet ely dependent on the presence of tyrosinase. Effects of the test agent s on the 221-cells were also observed in the absence of tyrosinase. Al though some of them were shown to be good substrates for tyrosinase on ly small changes in toxicity were observed as a result of the presence of the enzyme in comparison with 4HA. No direct correlation of the to xicity of the agents and COMT inhibition was observed. The possible mo de of action of the compounds through inhibition of COMT and interfere nce in melanogenesis is discussed together with other possibilities an d factors involved.