Ss. Deshpande et Gb. Maru, EFFECTS OF CURCUMIN ON THE FORMATION OF BENZO[ALPHA]PYRENE DERIVED DNA-ADDUCTS IN-VITRO, Cancer letters, 96(1), 1995, pp. 71-80
The effects of turmeric (T), curcumins (Cs), aqueous turmeric extract
(ATE) and curcumin-free aqueous turmeric extract (CFATE) on the format
ion of [H-3]benzo[a]pyrene ([H-3]B(a)P)-derived DNA adducts was studie
d in vitro employing mouse liver S9. A dose-dependent decrease in bind
ing of [H-3]B(a)P metabolites to calf thymus DNA was observed in the p
resence of T, Cs and ATE but not in the presence of CFATE, suggesting
curcumins to be active principles. Further studies employing mouse liv
er microsomes and individual components of curcumins, i.e. curcumin (C
), demethoxycurcumin (dmC) and bis-demethoxycurcumin (bdmC) showed tha
t all the three components brought about dose-dependent; inhibition of
[H-3]B(a)P-DNA adduct formation and inhibitory activity was in the or
der C > dmC > bdmC, investigations on the inhibitory effect of curcumi
n showed a dose-dependent decrease in cytochrome P450 and aryl hydroca
rbon hydroxylase (AHH) activity resulting in relatively larger amounts
of unmetabolized B(a)P in the presence of curcumin. Comparison of str
uctures of curcumins with their activity profile suggested the importa
nce of both parahydroxy (p-OH) and methoxy groups (-OCH3) in the struc
ture activity relationship. Experiments to study the mechanism of acti
on of curcumin indicated that the presence of curcumin was essential f
or the inhibitory effect, as removal of curcumin resulted in restorati
on of cytochrome P450 activity and the levels of [H-3]-B(a)P-DNA adduc
ts to control values. The present studies demonstrate that curcumin is
effective in inhibiting [H-3]B(a)P derived DNA adducts by interfering
with the metabolic enzymes and its physical presence is essential for
this effect.