Carcinogenesis, Vol 19, 1357-1360, Copyright © 1998 by Oxford University Press
SV Singh, X Hu, SK Srivastava, M Singh, H Xia, JL Orchard and HA Zaren
Curcumin (diferuloylmethane), the major yellow pigment in turmeric, has
been shown to inhibit benzo[a]pyrene (BaP)-induced forestomach cancer in
mice through mechanism(s) not fully understood. It is well known that while
cytochrome P4501A1 (CYP1A1) and epoxide hydrolase (EH) are important in the
conversion of BaP to its activated form, (+)-anti-7,8-
dihydroxy-9,10-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene [(+)-anti-BaPDE], the
detoxification of (+)-anti-BaPDE is accomplished by glutathione (GSH)
S-transferases (GST). Therefore, it seems reasonable to postulate that
curcumin may exert anti-carcinogenic activity either by inhibiting
activation of BaP or (and) by enhancing the detoxification of (+)-anti-
BaPDE. Administration p.o. of 2% curcumin in the diet to female A/J mice
for 14 days, which has been shown to cause a significant inhibition in
BaP-induced forestomach tumorigenesis, resulted in a modest but
statistically significant reduction in hepatic ethoxyresorufin O-deethylase
(EROD) activity, a reaction preferentially catalyzed by CYP1A1. While EROD
activity could not be detected in the forestomach of either control or
treated mice, curcumin feeding caused a statistically significant increase
(approximately 2.3-fold) in hepatic EH and GST activities. Hepatic and
forestomach GSH levels, and forestomach EH and GST activities were not
affected by curcumin treatment. Even though the levels of various hepatic
GST isoenzymes were significantly increased upon curcumin feeding, maximum
induction was noticed for the pi class isoenzyme (mGSTP1-1), which among
murine hepatic GSTs is highly efficient in the detoxification of (+)-anti-
BaPDE. In conclusion, the results of the present study suggest that
curcumin may inhibit BaP-induced forestomach cancer in mice by affecting
both activation as well as inactivation pathways of BaP metabolism in the
liver.
ARTICLES
Mechanism of inhibition of benzo[a]pyrene-induced forestomach cancer in mice by dietary curcumin
Cancer Research Laboratory, Mercy Cancer Institute, Pittsburgh, PA 15219, USA.
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