M. Kawase et al., RELATIONSHIP BETWEEN RADICAL INTENSITY AND CYTOTOXIC ACTIVITY OF DOPAMINE-RELATED COMPOUNDS, Anticancer research, 18(2A), 1998, pp. 1069-1074
Millimolar concentrations of dopamine (DA), norepinephrine (NE), and 3
,4-dihydroxyphenylacetic acid (DOPAC) were cytotoxic to human promyelo
cytic leukemic HL-60 cells. However, their metabolites (3,4-dihydroxym
andelic acid (DOMA), 3-methoxytyramine (MT), normetanephrine (NMN)) an
d six synthetic derivatives (which have two OCH3 groups replacing two
OH groups on catechol backbone) displayed much lower cytotoxic activit
y. Three active compounds, but not other less potent compounds, produc
ed radicals under alkaline conditions. All active compounds significan
tly enhanced the decay of ascorbic acid endogenously present in rat br
ain homogenate, whereas all synthetic derivatives were inactive. Ascor
bic 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.