Inhibitory effect of DL-butionine sulfoximine on P-glycoprotein activity in vitro

Abstract

Background. P-glycoprotein (Pgp) is a multidrug resistance protein 1 with broad substrate specificity. Its functioning can change under the influence of various substances, so the search for endogenous and exogenous compounds that modulate the activity of the transporter protein is an important area of research.
 Aim. To evaluate the effect of DL-butionine sulfoximine on the activity and amount of the Pgp transporter protein in Caco-2 cells.
 Material and methods. The study was performed on a human colon adenocarcinoma cell line (Caco-2). Cells were incubated with DL-butionine sulfoximine and quinidine (a classical Pgp inhibitor) at concentrations of 1, 5, 10, 50, 100, and 500 M for 3 hours. Pgp activity was evaluated by the transport of its substrate, fexofenadine, which concentration was determined by high performance liquid chromatography with ultraviolet detection (Stayer, Russia). The results were analyzed using StatSoft Statistica 13.0 (ANOVA), IC50 was calculated using GraphPad Prism 8 software. Differences were considered statistically significant at p 0.05.
 Results. Incubation with DL-butionine sulfoximine and quinidine at concentrations of 1500 M for 3 hours did not affect the amount of Pgp in Caco-2 cells. Pgp activity decreased when using DL-butionine sulfoximine at concentrations of 50500 M by a maximum of 47.7% (p=0.040). Quinidine at concentrations of 5500 M reduced Pgp activity by a maximum of 79.1% (p=0.0002) at a concentration of 500 M. Quinidine inhibited Pgp activity at lower concentrations compared to DL-butionine sulfoximine: the IC50 of fexofenadine with quinidine was 5.160.59 mol/l, for DL-butionine sulfoximine it was 17.212.46 mol/l (p= 0.001).
 Conclusion. DL-butionine sulfoximine has a direct inhibitory effect on the activity of the Pgp transporter protein on the Caco-2 cell line.