Evaluating the Inhibitory Potential of Phytochemicals on Species-specific Breast Cancer Resistance Protein Transport Activity

Inhibition of ATP-binding cassette (ABC) transporters is a common mechanism underlying pharmacokinetic interactions between xenobiotics (for example, drug-herb, herb-herb and herb-nutrient interactions). ABCG2, or Breast Cancer Resistance Protein (BCRP), is an efflux transporter located on a variety of cells, playing a key role in maintaining the barrier function of organs. We determined the inhibitory potential of eight phytochemicals on BCRP activity, in vitro, using membrane vesicles engineered to express species- specific BCRP.

Phytochemicals were selected based on their relevance for both human and animal health. Membrane vesicles were isolated from transduced human embryonic kidney (HEK) 293 cells, overexpressing BCRP with a human, bovine, caprine or ovine gene sequence. The inhibitory potential of 200 microM allyl methyl sulfide (in garlic), anethole (in anise), apigenin (in camomile), berberine (in goldenseal), carvacrol (in oregano), kaempferol (in chicory), quercetin (abundant in green plants and fruits) and N-isobutyldodeca- 2E,4E,8Z,10E/Z-tetraenamide (in Echinacea angustifolia), on the transport of the model BCRP-substrate [³H]-estrone-3-sulphate, was evaluated. Compounds were considered inhibitors when uptake was reduced by more than 30%. Five of the eight phytochemicals showed potential clinically relevant inhibition in all four species. These phytochemicals are now being compared for their inhibitory potency between species.

To our knowledge this is the first study where differences in the inhibitory potential of phytochemicals interacting with BCRP transport in human and dairy animals are being investigated. Our assay will give insight into the extrapolation of data between species and improve the ease of assessing safe and effective herbal use in humans and dairy animals.

Publication History

Article published online:
16 November 2023