Inhibition of the efflux of glutathione S-conjugates by plant polyphenols.

Abstract

The formation of dinitrophenylglutathione (DNP-SG) in human colon adenocarcinoma cells was identified and quantified by an HPLC-UV method, following exposure to 1-chloro-2,4-dinitrobenzene (CDNB) at 10 degrees for 40 min. The rate of efflux of DNP-SG at 37 degrees likewise, was measured by monitoring the DNP-SG content in the extracellular medium. Among the polyphenols examined for their action on DNP-SG export, butein was the most potent inhibitor with an IC50 value of 15 microM. The others, in order of decreasing potencies, were quercetin, tannic acid, 2'-hydroxychalcone, 2-hydroxychalcone anIIC50 values in the micromolar range. These polyphenols did not affect the ATP or the glutathione content of the cells. Mg(2+)-ATPase extracted from the plasma membrane of the cells was activated by DNP-SG in a concentration-dependent manner, and the reaction showed saturation kinetics with K(m) and Vmax values of 110 microM and 12.3 nmol/min/mg protein, respectively. However, the six polyphenols mentioned above had negligible effects on the Mg(2+)-ATPase activity, suggesting that this was probably not the target of their inhibitory action. Probenecid, p-trifluoromethoxy-phenylhydrazone (FCCP) and chlorambucil also showed varying degrees of inhibition of the export of DNP-SG.

• Authors: K Zhang, K P Wong
• Journal: Biochemical pharmacology (Biochem Pharmacol) Vol. 52 Issue 10 Pg. 1631-8 (Nov 22 1996) ISSN: 0006-2952 [Print] England
• PMID: 8937479 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Chalcones
• Flavonoids
• Hydrolyzable Tannins
• Phenols
• Polymers
• S-(2,4-dinitrophenyl)glutathione
• butein
• Chalcone
• Adenosine Triphosphate
• morin
• Quercetin
• Glutathione Transferase
• Ca(2+) Mg(2+)-ATPase
• Glutathione
• 2'-hydroxychalcone

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 1 (metabolism)
• Adenosine Triphosphate (metabolism)
• Biological Transport, Active (drug effects)
• Ca(2+) Mg(2+)-ATPase (metabolism)
• Cell Membrane (drug effects, enzymology)
• Chalcone (analogs & derivatives, pharmacology)
• Chalcones
• Flavonoids (pharmacology)
• Glutathione (analogs & derivatives, metabolism)
• Glutathione Transferase (metabolism)
• Humans
• Hydrolyzable Tannins (pharmacology)
• Kinetics
• Phenols (pharmacology)
• Plants
• Polymers (pharmacology)
• Quercetin (pharmacology)
• Tumor Cells, Cultured