Relationship between radical intensity and cytotoxic activity of dopamine-related compounds

Millimolar concentrations of dopamine (DA), norepinephrine (NE), and 3,4-dihydroxyphenylacetic acid (DOPAC) were cytotoxic to human promyelocytic leukemiC HL-60 cells. However, their metabolites (3,4-dihydroxymandelic acid (DOMA), 3-methoxytyramine (MT), normetanephrine (NMN)) and six synthetic derivatives (which have two OCH3 groups replacing two OH groups on catechol backbone) displayed much lower cytotoxic activity. Three active compounds, but not other less potent compounds, produced radicals under alkaline conditions. All active compounds significantly enhanced the decay of ascorbic acid endogenously present in rat brain homogenate, whereas all synthetic derivatives were inactive. Ascorbic acid induced apoptotic cell death in HL-60 cells and the apoptosis induction was significantly reduced by simultaneous addition of (DA). The cytotoxic activity of (DA) was also neutralized by ascorbic acid. These data suggest the possible interaction between (DA) and ascorbic acid.