Pharmacogenomics and Personalized Medicine
Open access peer-reviewed scientific and medical journals.
Dove Medical Press is now a member of the Open Access Initiative
An Author's Guide
A guide to help authors get their paper published.
Support Open Access and Dove Press
Promotional Article Monitoring - further details
Favored Author Program
Real benefits for authors, including fast-track processing of papers.
Sulfation of fulvestrant by human liver cytosols and recombinant SULT1A1 and SULT1E1
(3214) Total Article Views
Authors: Edavana VK, Yu X, Dhakal IB, Williams S, Ning B, Cook IT, Caldwell D, Falany CN, Kadlubar S
Published Date November 2011
Volume 2011:4 Pages 137 - 145
Vineetha Koroth Edavana1, Xinfeng Yu1, Ishwori B Dhakal1, Suzanne Williams1, Baitang Ning2, Ian T Cook3, David Caldwell1, Charles N Falany3, Susan Kadlubar1
1Division of Medical Genetics, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA; 2Division of Personalized Nutrition and Medicine, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR, USA; 3Department of Pharmacology, University of Alabama, Birmingham, AL, USA
Abstract: Fulvestrant (Faslodex™) is a pure antiestrogen that is approved to treat hormone receptor-positive metastatic breast cancer in postmenopausal women. Previous studies have demonstrated that fulvestrant metabolism in humans involves cytochromes P450 and UDP-glucuronosyltransferases (UGTs). To date, fulvestrant sulfation has not been characterized. This study examined fulvestrant sulfation with nine recombinant sulfotransferases and found that only SULT1A1 and SULT1E1 displayed catalytic activity toward this substrate, with Km of 4.2 ± 0.99 and 0.2 ± 0.16 µM, respectively. In vitro assays of 104 human liver cytosols revealed marked individual variability that was highly correlated with β-naphthol sulfation (SULT1A1 diagnostic substrate; r = 0.98, P < 0.0001), but not with 17ß-estradiol sulfation (SULT1E1 diagnostic substrate; r = 0.16, P = 0.10). Fulvestrant sulfation was correlated with both SULT1A1*1/2 genotype (P value = 0.023) and copy number (P < 0.0001). These studies suggest that factors influencing SULT1A1/1E1 tissue expression and/or enzymatic activity could influence the efficacy of fulvestrant therapy.
Keywords: fulvestrant, sulfotransferase, genotype, copy number
Cannotea Citeulike Del.icio.us Facebook LinkedIn Twitter
Other articles by Dr Susan Kadlubar
Readers of this article also read:
Call For Submissions
Submit Original Research Article, Review, Case Report, or Rapid Communication in Pharmacogenomics and Personalized Medicine
- Enzalutamide: an evidence-based review of its use in the treatment of prostate cancer
- The benefits and risks of testosterone replacement therapy: a review
- Tumor necrosis factor-alpha inhibitor treatment for sarcoidosis
- Tenofovir-associated bone density loss