Analysis of the oxidative catabolism of retinoic acid in rat Dunning R3327G prostate tumors.
We studied the enzymatic characteristics of the oxidative catabolism of retinoic acid (RA) and its inhibition by liarozole-fumarate in homogenates of rat Dunning R3327G prostate tumors. Homogenates of rat liver were used as reference material. Both tumor and liver homogenates were able to catabolize retinoic acid. HPLC analysis revealed only very polar metabolites in tumors, while in the liver both metabolites with intermediate polarity and more polar metabolites were found. Kinetic analysis of retinoic acid catabolism showed a K(m) of 1.7 +/- 0.7 microM and a Vmax of 4.2 +/- 4.4 pmol polar RA metabolites/mg protein/hr for Dunning G tumor homogenates. In liver homogenates a K(m) value of 4.3 +/- 0.5 microM and a Vmax value of 290 +/- 120 pmol polar RA metabolites/mg protein/hr were obtained. Liarozole-fumarate inhibited retinoic acid catabolism in Dunning tumors and liver with IC50 values of 0.26 +/- 0.16 microM and 0.14 +/- 0.05, respectively. The results suggest that rat Dunning R3327G tumors are able to metabolize retinoic acid in a manner similar to that found in rat liver but with a lower metabolizing capacity.
Krekels
M D
MD
Department of Endocrino- and Immunopharmacology, Janssen Research Foundation, Beerse, Belgium.
Zimmerman
J
J
Janssens
B
B
Van Ginckel
R
R
Cools
W
W
Van Hove
C
C
Coene
M C
MC
Wouters
W
W
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D007093:Imidazoles / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D008297:Male; D009249:NADP / Q000494:pharmacology; D010084:Oxidation-Reduction; D011471:Prostatic Neoplasms / Q000201:enzymology*; D051381:Rats; D017208:Rats, Wistar; D014212:Tretinoin / Q000378:metabolism*
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D007093:Imidazoles; D009249:NADP; D014212:Tretinoin; C061121:liarozole