Sulfation disposition of liquiritigenin in SULT1A3 overexpressing HEK293 cells: The role of breast cancer resistance protein (BCRP) and multidrug resistance-associated protein 4 (MRP4) in sulfate efflux of liquiritigenin

• Published in: European journal of pharmaceutical sciences 2018-11, Vol.124, p.228-239
• Main Authors: Liu, Tong, Zhang, Xiaojing, Zhang, Yidan, Hou, Jiuzhou, Fang, Dong, Sun, Hua, Li, Qin, Xie, Songqiang
• Format: Article
• Language: English
• Subjects: ATP Binding Cassette Transporter, Subfamily G, Member 2 - metabolism; Efflux transporter; Flavanones - pharmacology; HEK293 Cells; Humans; Liquiritigenin; Multidrug Resistance-Associated Proteins - metabolism; Neoplasm Proteins - metabolism; Sulfates - metabolism; Sulfonation; Sulfotransferase; Sulfotransferases - metabolism
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2018.08.041

This study aimed to investigate the cellular disposition of liquiritigenin via the sulfonation pathway and the role of efflux transporters in liquiritigenin sulfate excretion. The sulfonation disposition of liquiritigenin was investigated using SULT1A3 overexpressed HEK293 cells (HEK-SULT1A3 cells). Liquiritigenin generated one mono-sulfate metabolite (7-O-sulfate) in HEK-SULT1A3 cell lysate. And the sulfonation followed the Michaelis-Menten kinetic (Vmax = 0.84 nmol/min/mg and Km = 7.12 μM). Expectedly, recombinant SULT1A3 (hSULT1A3) showed a highly similar kinetic profile with cell lysate. Furthermore, 7-O-sulfate was rapidly generated and excreted in HEK-SULT1A3 cells. Ko143 (a BCRP-selective inhibitor) at 20 μM significantly decreased the excretion rate of liquiritigenin sulfate (>42.5%, p 97.4%, p