INTERACTIONS OF BIOFLAVONOID ROBININ WITH EFFLUX TRANSPORTERS: P-GLYCOPROTEIN AND BREAST CANCER RESISTANCE PROTEIN

Present study investigated the possible role of P-glycoprotein in intracellular exposure of active substance (robinin) natural medicine Flaroninum™ and effect robinin on cellular accumulation mitoxantrone either BCRP-overexpressing BCRP-negative cells. Robinin - kaempferol-3-O-b-D-robinoside-7-O-α-L-rhamnopyranoside, has been obtained from over ground parts Astragalus falcatus Lam., growing Georgia. The compound possesses hypoazotemic diuretic activities is proposed for complex therapy kidney diseases. P-gp-overexpressing P-gp-negative human breast cancer cells (MCF7) were used to examine absorption character kaempferol with or without verapamil (P-gp inhibitor). Flavonoids concentrations determined by LC/MS/MS. transport was P-gp-dependent significantly increased extent uptake cells, which attributed part P-gp-inhibition verapamil. When comparing aglycone we found that greater than robinin. Since some glycosylated forms flavonoids have been demonstrated to suppress resistance protein (BCRP/ABCG2), hypothesized kaempferol-3-O-b-D-robinoside-7-O-α-L-rhamnopyranoside may act as a BCRP-inhibitor. Mitoxantrone studies performed MCF7 using flow cytometric analysis. (5 50 mM) had no significant impacts BCRP-mediated transport; contrary, produced mitoxantrone. From these results, suggest component Flaroninum™, robinin, may be a substrate of P-gp its efflux outside mediated P-gp contribute decreased concentration.