Goldenseal (Hydrastis canadensis) 43525850
Identification of novel dietary phytochemicals inhibiting the efflux transporter breast cancer resistance protein (BCRP/ABCG2) CSV JSON

Breast cancer resistance protein (BCRP/ABCG2) plays an important role in determining the absorption and disposition of consumed xenobiotics including various drugs and dietary phytochemicals and is also one of the prominent efflux transporters involved in multidrug resistance (MDR). In this study, we have investigated the interactions between ABCG2 and 56 naturally-occurring phytochemicals including phenolic acids, flavonoids, triterpenes and other common dietary phytochemicals, as well as two non plant-based compounds (hippuric acid and propyl gallate) using cell- and membrane-based transport inhibition assays. Of the non-flavonoid phytochemicals tested, berberine, celastrol, ellagic acid, limonin, oleanolic acid, propyl gallate, sinapic acid and ursolic acid demonstrated significant inhibition of ABCG2- mediated transport. Chrysoeriol, laricitrin, myricetin 30,40,50-trimethylether, pinocembrin, quercitrin, tamarixetin, tricetin and tricetin 30,40,50-trimethylether were also identified as novel flavonoid ABCG2 inhibitors. The identified inhibitory activity of dietary phytochemicals on ABCG2 provides a framework for further investigation of ABCG2-modulated phytochemical bioavailability, MDR, and possible food– drug interactions.

1 . Inhibition of BCRP by Berberine (id=NPDI-YlLZrw)

In Vitro Transporter Inhibition Experiment

Inhibition was detected.  Cutoff used — not specified

mitoxantrone

Berberine 19012197

  • BCRP (ABCG2)

Transfected / siRNA knock-out / injected cells HEK293 transfected cells

Results

Table 2 - significance not mentioned so assumed to be not significant

Compound measured Measurement Value Study sequence Additional information N replicates

Experimental Conditions

Cell Culture Conditions

7 x 10^5 cells/mL

200 μg/mL

Assay Conditions

90 min

37 deg C

5 μM

50 μM

Sigma–Aldrich, Auckland, NZ

1 . BCRP inhibition measured by accumulation (id=NPDI-jCImIg)

In Vitro Transporter Kinetics Experiment

Transport Activity was detected.  Cutoff used — not specified

mitoxantrone

  • BCRP (ABCG2)

Transfected / siRNA knock-out / injected cells HEK293 transfected cells

Results

Table 1 - Values are expressed as percentage of control, mean ± SEM, n ≥ 4 for mitoxantrone accumulation

Compound measured Measurement Value Study sequence Additional information N replicates

Experimental Conditions

Cell Culture Conditions

7 x 10^5 cells/mL

200 μg/mL

Assay Conditions

90 min

37 deg C

5 μM