title: Sulfation of afimoxifene, endoxifen, raloxifene, and fulvestrant by the human cytosolic sulfotransferases (SULTs): A systematic analysis.
abstract: Previous studies demonstrated that sulfate conjugation is involved in the metabolism of three commonly used breast cancer drugs, tamoxifen, raloxifene and fulvestrant. The current study was designed to systematically identify the human cytosolic sulfotransferases (SULTs) that are capable of sulfating raloxifene, fulvestrant, and two active metabolites of tamoxifen, afimoxifene and endoxifen. A systematic analysis using 13 known human SULTs revealed SULT1A1 and SULT1C4 as the major SULTs responsible for the sulfation of afimoxifene, endoxifen, raloxifene and fulvestrant. Kinetic parameters of these two human SULTs in catalyzing the sulfation of these drug compounds were determined. Sulfation of afimoxifene, endoxifen, raloxifene and fulvestrant under metabolic conditions was examined using HepG2 human hepatoma cells and MCF-7 breast cancer cells. Moreover, human intestine, kidney, liver, and lung cytosols were examined to verify the presence of afimoxifene/endoxifen/raloxifene/fulvestrant-sulfating activity.
authors.affiliation: Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo Health Science Campus, Toledo, OH, 43614, USA; Department of Obstetrics and Gynecology, Beijing Hospital, Beijing, 100730, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Hui
authors.affiliation: Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo Health Science Campus, Toledo, OH, 43614, USA; School of Pharmacy, North Sichuan Medical College, Nanchong, Sichuan, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Luo
authors.affiliation: Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo Health Science Campus, Toledo, OH, 43614, USA.
authors.forename: Lingtian
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Biochemistry and Applied Biosciences, University of Miyazaki, Miyazaki, 889-2192, Japan.
authors.forename: Katsuhisa
authors.initials: K
authors.lastname: Kurogi
authors.affiliation: Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo Health Science Campus, Toledo, OH, 43614, USA; School of Pharmacy, North Sichuan Medical College, Nanchong, Sichuan, China.
authors.forename: Chunyang
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Biochemistry and Applied Biosciences, University of Miyazaki, Miyazaki, 889-2192, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Sakakibara
authors.affiliation: Biochemistry and Applied Biosciences, University of Miyazaki, Miyazaki, 889-2192, Japan.
authors.forename: Masahito
authors.initials: M
authors.lastname: Suiko
authors.affiliation: Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo Health Science Campus, Toledo, OH, 43614, USA. Electronic address: ming.liu@utoledo.edu.
authors.forename: Ming-Cheh
authors.initials: MC
authors.lastname: Liu
mesh_terms: D002384:Catalysis; D003600:Cytosol / Q000201:enzymology*; D004958:Estradiol / Q000031:analogs & derivatives* / Q000378:metabolism; D000077267:Fulvestrant; D056945:Hep G2 Cells; D006801:Humans; D061986:MCF-7 Cells; D020849:Raloxifene Hydrochloride / Q000378:metabolism*; D013431:Sulfates; D015238:Sulfotransferases / Q000502:physiology*; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D013431:Sulfates; D013629:Tamoxifen; C016601:afimoxifene; D000077267:Fulvestrant; C055492:4-hydroxy-N-desmethyltamoxifen; D020849:Raloxifene Hydrochloride; D004958:Estradiol; D015238:Sulfotransferases
keywords: Afimoxifene; Cytosolic sulfotransferase; Endoxifen; Fulvestrant; Raloxifene; SULT; Sulfation