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United States Department of Agriculture

Agricultural Research Service

Research Project: Rice as a Source and Delivery System for Nutrients and Lipophilic Bioactive Compounds

Location: Food Processing and Sensory Quality Research

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

Authors
item Chimezie, Chukwuemezie -
item Stratford, Eobert -
item Omari, Christopher -
item Skripnikova, Elena -
item Townley, Ian -
item Ewing, Adina -
item Glotser, Elena -
item Quadri, Syeda -
item Cole, Richard -
item Boue, Stephen

Submitted to: Journal of Medicinal Foods
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: October 24, 2013
Publication Date: January 10, 2014
Citation: Chimezie, C., Stratford, E.E., Omari, C.F., Skripnikova, E., Townley, I., Ewing, A.C., Glotser, E., Quadri, S.S., Cole, R.B., Boue, S.M. 2014. Glyceollin transport, metabolism, and effects on P-glycoprotein function in Caco-2 cells . Journal of Medicinal Foods. 17(4):462-471.

Interpretive Summary: Glyceollins are phytoalexins (induced during stress) produced in soybeans. Their impressive anti-cancer 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 transport proteins in human colon cancer (Caco-2) cells. Results suggest high absorption potential of glyceollin by a passive diffusion dominated mechanism. Also, a sulfate group added to glyceollin was detected after glyceollin was added to Caco-2 cells. Our 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; furthermore, they indicate that glyceollin, again similar to genistein, does not appear to alter the efflux transport protein (Pgp) in Caco-2 cells.

Technical Abstract: Glyceollins are phytoalexins produced in soybeans from their isoflavone precursor daidzein. Their impressive anti-cancer 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 in Caco-2 cells. At 10 and 25 µM, glyceollin permeability was 2.4 ± 0.16 x 10-4 cm/s and 2.1 ± 0.15 x 10-4 cm/s, respectively, in the absorptive direction. Basolateral to apical permeability at 25 µM was 1.6 ± 0.10 x 10-4 cm/s. Results suggest high absorption potential of glyceollin by a passive diffusion dominated mechanism. A sulfate conjugate at the phenolic hydroxy position was observed following exposure to Caco-2 cells. In contrast to verapamil inhibition of the net secretory permeability of rhodamine 123, and its enhancement of calcein AM uptake into Caco-2 cells, neither glyceollin nor genistein inhibited P-gp up to 300 µM. Exposure to 100 µM rifampin for 24 hours induced ABCB1 mRNA expression in Caco-2, and stimulated R123 secretory transport 35 ± 10.1% relative to control, there was no significant change in ABCB1 mRNA expression or R123 transport in cells exposed to glyceollin or genistein 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; furthermore, they indicate that glyceollin, again similar to genistein, does not appear to alter Pgp function in Caco-2 cells.

Last Modified: 10/24/2014
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