Premium
16α‐Hydroxyestrone Inhibits Estrogen Sulfotransferase Activity in Human Liver Cancer Cells
Author(s) -
Campisi Ildegarda,
Granata Orazia M.,
Cocciadiferro Letizia,
Calabrò Maurizio,
Polito Lucia M.,
Carruba Giuseppe
Publication year - 2009
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2008.03694.x
Subject(s) - estrogen , estrogen receptor , transactivation , endocrinology , medicine , antiestrogen , tamoxifen , chemistry , selective estrogen receptor modulator , sulfotransferase , estrogen receptor beta , estrogen receptor alpha , biology , cancer , biochemistry , breast cancer , transcription factor , sulfation , gene
In this study we investigated the impact of estrogen antagonists and of 16α‐OHE1 (an estrogen derivative that binds to and induces transactivation of estrogen receptors) on estrogen metabolism in malignant HepG2 human liver cells featured by high estrogen sulfotransferase (EST); our aim was to clarify the potential correlation of EST and ER. As expected, the HepG2 cells exhibited a very high EST activity, with the majority of estrogen metabolites (over 86%) being detected as sulfates by 24 h. The coincubation of E2 and the antiestrogen tamoxifen induced a weak inhibition of EST activity (from 85.4% to 81.5%), while the coincubation with the pure antagonist ICI‐182 and with 16α‐OHE1 produced a 50% and 90% decrease of EST, respectively. Interestingly, both selective estrogen receptor modulators (SERMs) TAM and ICI‐182, along with the same 16α‐OHE1, gave rise respectively to a 2.8%, 3.2%, and 4.6% of de novo 16α‐OHE1 formation. The inhibition of EST and the increase of 16α‐OHE1 formation were both time‐ and dose‐dependent. Our results suggest that EST activity is tightly associated with ER transactivation and can be regulated by selective estrogen receptor modulators (SERMs), including antiestrogens and 16α‐OHE1. In this framework, 16α‐OHE1 may have a potential role in human liver carcinogenesis, also through the inhibition of EST and the production of unconjugated, bioavailable estrogens.