Glyceollin transport, metabolism, and effects on P-glycoprotein function in Caco-2 cells

Chukwuemezie Chimezie, Adina C. Ewing, Syeda S. Quadri, Richard B. Cole, Stephen M. Boué, Christopher F. Omari, Melyssa Bratton, Elena Glotser, Elena Skripnikova, Ian Townley, Robert E. Stratford

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7 Scopus citations

Abstract

Glyceollins are phytoalexins produced in soybeans from their isoflavone precursor daidzein. Their impressive anticancer and glucose normalization effects in rodents have generated interest in their therapeutic potential. The aim of the present studies was to begin to understand glyceollin intestinal transport and metabolism, and their potential effects on P-glycoprotein (Pgp) in Caco-2 cells. At 10 and 25 μM, glyceollin permeability was 2.4±0.16×10-4 cm/sec and 2.1±0.15×10 -4 cm/sec, respectively, in the absorptive direction. Basolateral to apical permeability at 25 μM was 1.6±0.10×10-4 cm/sec. Results suggest high absorption potential of glyceollin by a passive-diffusion-dominated mechanism. A sulfate conjugate at the phenolic hydroxyl position was observed following exposure to Caco-2 cells. In contrast to verapamil inhibition of the net secretory permeability of rhodamine 123 (R123) and its enhancement of calcein AM uptake into Caco-2 cells, neither glyceollin nor genistein inhibited Pgp (MDR1; ABCB1) up to 300 μM. There was no significant change in MDR1 mRNA expression, Pgp protein expression, or R123 transport in cells exposed to glyceollin or genistein for 24h up to 100 μM. Collectively, these results suggest that glyceollin has the potential to be well absorbed, but that, similar to the isoflavone genistein, its absorption may be reduced substantially by intestinal metabolism; further, they indicate that glyceollin does not appear to alter Pgp function in Caco-2 cells.

Original languageEnglish (US)
Pages (from-to)462-471
Number of pages10
JournalJournal of Medicinal Food
Volume17
Issue number4
DOIs
StatePublished - Apr 1 2014

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Keywords

  • diet
  • flavonoids
  • genistein
  • glyceollin
  • induction of Pgp
  • inhibition of Pgp
  • isoflavone
  • phytoestrogen

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

Cite this

Chimezie, C., Ewing, A. C., Quadri, S. S., Cole, R. B., Boué, S. M., Omari, C. F., Bratton, M., Glotser, E., Skripnikova, E., Townley, I., & Stratford, R. E. (2014). Glyceollin transport, metabolism, and effects on P-glycoprotein function in Caco-2 cells. Journal of Medicinal Food, 17(4), 462-471. https://doi.org/10.1089/jmf.2013.0115