Effects of turmeric on the activities of benzo(a)pyrene-induced cytochrome P-450 isozymes.
Turmeric and/or its main coloring component, curcumin (diferuloylmethane), have been shown to inhibit benzo(a)pyrene [B(a)P]-induced forestomach papillomas in mice. However, the mechanisms of turmeric-mediated chemoprevention are not well understood. To study the mechanisms of turmeric-mediated chemoprevention, we investigated the effects of turmeric feeding on the activities of isozymes of cytochrome P-450 (CYP450)--namely, ethoxyresorufin O-deethylase (EROD, CYP1A1) and methoxyresorufin O-demethylase (MROD, CYP1A2)--which are predominantly involved in the metabolism of B(a)P. We determined the activities of EROD and MROD by monitoring the formation of resorufin from respective substrates in the presence of microsomal proteins obtained from tissues of control, 1% turmeric, 1 mg B(a)P, and 1% turmeric + 1 mg B(a)P-fed Swiss mice. The results indicate that the administration of turmeric through diet significantly inhibited the activities of both EROD and MROD in forestomach (target organ), liver, and lung. In vitro studies employing curcumin, demethoxycurcumin, and bis-demethoxycurcumin suggest that curcumins are the inhibitors in turmeric. Inhibition of B(a)P metabolizing phase I enzymes (EROD, MROD) may be at least in part one of the possible modes of chemopreventive action of turmeric/curcumin.
Thapliyal
R
R
Carcinogenesis Division, Cancer Research Institute, Tata Memorial Centre, Parel, Mumbai, India.
Deshpande
S S
SS
Maru
G B
GB
D000818:Animals; D001564:Benzo(a)pyrene / Q000494:pharmacology*; D003474:Curcumin / Q000494:pharmacology*; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D010078:Oxazines / Q000378:metabolism; D010088:Oxidoreductases / Q000096:biosynthesis*
D010078:Oxazines; D001564:Benzo(a)pyrene; C014180:resorufin; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; C076307:methoxyresorufin-O-demethylase; D019363:Cytochrome P-450 CYP1A1; D003474:Curcumin