The effects of endoxifen and other major metabolites of tamoxifen on the sulfation of estradiol catalyzed by human cytosolic sulfotransferases hSULT1E1 and hSULT1A1*1.

ABSTRACT: Tamoxifen is successfully used for both treatment and prevention of estrogen-dependent breast cancer, yet side effects and development of resistance remain problematic. Endoxifen is a major active metabolite of tamoxifen that is being investigated for clinical use. We hypothesized that endoxifen and perhaps other major metabolites of tamoxifen may affect the ability of human estrogen sulfotransferase 1E1 (hSULT1E1) and human phenol sulfotransferase 1A1 isoform 1 (hSULT1A1*1) to catalyze the sulfation of estradiol, an important mechanism in termination of estrogen signaling through loss of activity at estrogen receptors. Our results indicated that endoxifen, N-desmethyltamoxifen (N-desTAM), 4-hydroxytamoxifen (4-OHTAM), and tamoxifen-N-oxide were weak inhibitors of hSULT1E1 with Ki values r

SUBMITTER: Squirewell EJ 

PROVIDER: S-EPMC4429681 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature