Journal article
The sulfated conjugate of biochanin A is a substrate of breast cancer resistant protein (ABCG2)
Biopharmaceutics & drug disposition, Vol.32(8), pp.446-457
11/2011
DOI: 10.1002/bdd.772
PMID: 21910126
Abstract
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. Copyright © 2011 John Wiley & Sons, Ltd.
Details
- Title: Subtitle
- The sulfated conjugate of biochanin A is a substrate of breast cancer resistant protein (ABCG2)
- Creators
- Guohua An - University at Buffalo, State University of New YorkMarilyn E Morris - University at Buffalo, State University of New York
- Resource Type
- Journal article
- Publication Details
- Biopharmaceutics & drug disposition, Vol.32(8), pp.446-457
- DOI
- 10.1002/bdd.772
- PMID
- 21910126
- NLM abbreviation
- Biopharm Drug Dispos
- ISSN
- 0142-2782
- eISSN
- 1099-081X
- Publisher
- John Wiley & Sons, Ltd; Chichester, UK
- Number of pages
- 12
- Grant note
- Susan G. Komen Breast Cancer Foundation (BCTR0601385)
- Language
- English
- Date published
- 11/2011
- Academic Unit
- Pharmaceutical Sciences and Experimental Therapeutics
- Record Identifier
- 9984065317802771
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