Celecoxib influences steroid sulfonation catalyzed by human recombinant sulfotransferase 2A1.

ABSTRACT: Celecoxib has been reported to switch the human SULT2A1-catalyzed sulfonation of 17?-estradiol (17?-E2) from the 3- to the 17-position. The effects of celecoxib on the sulfonation of selected steroids catalyzed by human SULT2A1 were assessed through in vitro and in silico studies. Celecoxib inhibited SULT2A1-catalyzed sulfonation of dehydroepiandrosterone (DHEA), androst-5-ene-3?, 17?-diol (AD), testosterone (T) and epitestosterone (Epi-T) in a concentration-dependent manner. Low ?M concentrations of celecoxib strikingly enhanced the formation of the 17-sulfates of 6-dehydroestradiol (6D-E2), 17?-dihydroequilenin (17?-Eqn), 17?-dihydroequilin (17?-Eq), and 9-dehydroestradiol (9D-E2) as well as the overall rate of sulfonation. For 6D-E2, 9D-E2 and 17?-Eqn, celecoxib inhibited 3-sulfonation, however 3-sulfonation of 17?-Eq was stimulated at celecoxib concentrations below 40 ?M. Ligand docking studies in silico suggest that celecoxib binds in the substrate-binding site of SULT2A1 in a manner that prohibits the usual binding of substrates but facilitates, for appropriately shaped substrates, a binding mode that favors 17-sulfonation.

SUBMITTER: Ambadapadi S 

PROVIDER: S-EPMC4501872 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature