The sulfated conjugate of biochanin A is a substrate of breast cancer resistant protein (ABCG2).

The aim of the study was to investigate the role of breast cancer resistance protein (BCRP, ABCG2) in the transport of biochanin A and its metabolites. Transport studies were carried out in MDCK/bcrp1 as well as in control cells, and samples were analysed for biochanin A aglycone and metabolites using LC/MS/MS. In bidirectional transport studies biochanin A sulfate was detected in both apical and basolateral chambers after the addition of biochanin A. Analysis by RT-PCR revealed that the enzyme sulfotransferase 1A1 is expressed in Madin-Darby canine kidney (MDCK)-II cells. After its intracellular formation, biochanin A sulfate was preferentially transported to the basolateral side in MDCK/Mock cells, whereas apical transport of biochanin A sulfate was predominant in MDCK/Bcrp1 cells. Genistein, an additional metabolite of biochanin A formed intracellularly, was also found to be a bcrp1 substrate. Studies with MDCK/MRP2 (ABCC2) cells demonstrated that both genistein and biochanin A sulfate are not MRP2 substrates. In contrast, biochanin A aglycone was not transported by murine or human BCRP; nor is it a substrate of MRP2 or P-glycoprotein. Therefore, BCRP may play an important role in the enteric cycling of biochanin A sulfate and through this mechanism may alter the bioavailability of its non-substrate parent compound biochanin A. Moreover, MDCK-II cells might be a suitable model to investigate the synergistic role of sulfotransferase enzymes with efflux transporters.