title: Human cytosolic sulfotransferase SULT1C4 mediates the sulfation of doxorubicin and epirubicin.
abstract: Doxorubicin, an anthracycline, has been reported to be excreted in sulfate conjugated form. The current study aimed to identify the human cytosolic sulfotransferase(s) (SULT(s)) that is(are) capable of sulfating doxorubicin and its analog epirubicin, and to verify whether sulfation of doxorubicin and epirubicin may occur under metabolic conditions. A systematic analysis of thirteen known human SULTs, previously cloned, expressed, and purified, revealed SULT1C4 as the only human SULT capable of sulfating doxorubicin and epirubicin. Cultured HepG2 human hepatoma cells and Caco-2 human colon carcinoma cells were labeled with [(35)S]sulfate in the presence of different concentrations of doxorubicin or epirubicin. Analysis of spent labeling media showed the generation and release of [(35)S]sulfated doxorubicin and epirubicin by HepG2 cells and Caco-2 cells. Reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed the expression of SULT1C4 in both HepG2 cells and Caco-2 cells. These results provided a molecular basis underlying the previous finding that sulfate-conjugated doxorubicin was excreted in the urine of patients treated with doxorubicin.
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; School of Pharmacy, North Sichuan Medical College, Nanchong, Sichuan, China.
authors.forename: Chunyang
authors.initials: C
authors.lastname: Zhou
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; Biochemistry and Applied Biosciences, University of Miyazaki, Miyazaki 889-2192, Japan.
authors.forename: Katsuhisa
authors.initials: K
authors.lastname: Kurogi
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: D018938:Caco-2 Cells; D003600:Cytosol / Q000201:enzymology*; D004317:Doxorubicin / Q000737:chemistry / Q000378:metabolism*; D015251:Epirubicin / Q000737:chemistry / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013431:Sulfates / Q000378:metabolism*; D015238:Sulfotransferases / Q000235:genetics / Q000378:metabolism*
chemical_list: D013431:Sulfates; D015251:Epirubicin; D004317:Doxorubicin; D015238:Sulfotransferases
keywords: Cytosolic sulfotransferase; Doxorubicin; Epirubicin; SULT; Sulfation