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

Biopharm Drug Dispos. 2011 Nov;32(8):446-57. doi: 10.1002/bdd.772. Epub 2011 Sep 11.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism*
  • Animals
  • Arylsulfotransferase / genetics
  • Arylsulfotransferase / metabolism
  • Biological Transport
  • Cell Line, Tumor
  • Dogs
  • Genistein / metabolism*
  • Humans
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Mice
  • Multidrug Resistance-Associated Proteins / genetics
  • Multidrug Resistance-Associated Proteins / metabolism
  • RNA, Messenger / metabolism
  • Sulfates / metabolism*
  • Transfection

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • Abcg2 protein, mouse
  • Isoenzymes
  • Multidrug Resistance-Associated Proteins
  • RNA, Messenger
  • Sulfates
  • multidrug resistance-associated protein 2
  • Genistein
  • Arylsulfotransferase
  • biochanin A