Glyceollin Effects on MRP2 and BCRP in Caco-2 Cells, and Implications for Metabolic and Transport Interactions

Chukwuemezie Chimezie, Adina Ewing, Chandler Schexnayder, Melyssa Bratton, Elena Glotser, Elena Skripnikova, Pedro Sá, Stephen Boué, Robert Stratford Jr.

Research output: Contribution to journalArticle

8 Scopus citations


Glyceollins are phytoalexins produced in soybeans under stressful growth conditions. On the basis of prior evaluations, they show potential to treat multiple diseases, including certain cancers, Type 2 diabetes, and cardiovascular conditions. The aim of the present study was to expand on recent studies designed to initially characterize the intestinal disposition of glyceollins. Specifically, studies were undertaken in Caco-2 cells to evaluate glyceollins' effects on apical efflux transporters, namely, MRP2 and BCRP, which are the locus of several intestinal drug-drug and drug-food interactions. 5- (and 6)-carboxy-2',7'-dichloroflourescein (CDF) was used to provide a readout on MRP2 activity, whereas BODIPY-prazosin provided an indication of BCRP alteration. Glyceollins were shown to reverse MRP2-mediated CDF transport asymmetry in a concentration-dependent manner, with activity similar to the MRP2 inhibitor, MK-571. Likewise, they demonstrated concentration-dependent inhibition of BCRP-mediated efflux of BODIPY-prazosin with a potency similar to that of Ko143. Glyceollin did not appreciably alter MRP2 or BCRP expression following 24 h of continuous exposure. The possibility that glyceollin mediated inhibition of genistein metabolite efflux by either transporter was evaluated. However, results demonstrated an interaction at the level of glyceollin inhibition of genistein metabolism rather than inhibition of metabolite transport.

Original languageEnglish (US)
Pages (from-to)972-981
Number of pages10
JournalJournal of Pharmaceutical Sciences
Issue number2
StatePublished - Feb 1 2016
Externally publishedYes



  • active transport
  • drug interaction
  • efflux pumps
  • flavonoids
  • food effects
  • genistein
  • glyceollin
  • intestinal absorption
  • intestinal metabolism
  • phytoestrogen

ASJC Scopus subject areas

  • Medicine(all)
  • Pharmaceutical Science

Cite this

Chimezie, C., Ewing, A., Schexnayder, C., Bratton, M., Glotser, E., Skripnikova, E., Sá, P., Boué, S., & Stratford Jr., R. (2016). Glyceollin Effects on MRP2 and BCRP in Caco-2 Cells, and Implications for Metabolic and Transport Interactions. Journal of Pharmaceutical Sciences, 105(2), 972-981.