Inhibitory effects of herbal extracts on breast cancer resistance protein (BCRP) and structure-inhibitory potency relationship of isoflavonoids.

@article{Tamaki2010InhibitoryEO,
  title={Inhibitory effects of herbal extracts on breast cancer resistance protein (BCRP) and structure-inhibitory potency relationship of isoflavonoids.},
  author={Hirofumi Tamaki and Hiroki Satoh and S. Hori and Hisakazu Ohtani and Yasufumi Sawada},
  journal={Drug metabolism and pharmacokinetics},
  year={2010},
  volume={25 2},
  pages={
          170-9
        }
}
The inhibition of intestinal breast cancer resistance protein (BCRP), which restricts the absorption of xenobiotics, may increase the systemic availability of its substrates. The aim of this study was to evaluate the inhibitory effects of herbal extracts and their constituents on BCRP-mediated transport. The inhibitory effects of 9 herbal extracts and 23 isoflavonoids, including soybean-derived isoflavones, on BCRP-mediated methotrexate (MTX) transport were evaluated using BCRP-expressing… 

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References

SHOWING 1-10 OF 59 REFERENCES

Inhibitory Effects of Terpenoids on Multidrug Resistance-Associated Protein 2- and Breast Cancer Resistance Protein-Mediated Transport

The findings suggest that glycyrrhetic acid and abietic acid can potently inhibit MRP2- or BCRP-mediated membrane transport and may interact with their substrates in pharmacokinetic processes.

Effects of the Flavonoid Chrysin on Nitrofurantoin Pharmacokinetics in Rats: Potential Involvement of ABCG2

The results indicate that the flavonoid chrysin significantly inhibits nitrofurantoin transport mediated by human BCRP and murine Bcrp1.

Flavonoids are inhibitors of breast cancer resistance protein (ABCG2)-mediated transport.

The results obtained in this study could be clinically relevant in terms of both MDR reversal in cancer treatment and drug-flavonoid pharmacokinetic interactions.

Flavonoids inhibit breast cancer resistance protein-mediated drug resistance: transporter specificity and structure–activity relationship

The present results indicate that many flavonoids selectively inhibit BCRP only and examined the structure–BCRP inhibitory activity relationship from the current study.

Phytoestrogens/Flavonoids Reverse Breast Cancer Resistance Protein/ABCG2-Mediated Multidrug Resistance

This study shows that phytoestrogens/flavonoids, such as genistein, naringenin, acacetin, and kaempferol, potentiated the cytotoxicity of SN-38 and mitoxantrone in BCRP-transduced K562 (K562/BCRP) cells and suggests that flavonoid and glycosylated flavonoids may be useful in overcoming B CRP-mediated drug resistance in tumor cells.

Flavonoid structure-activity studies identify 6-prenylchrysin and tectochrysin as potent and specific inhibitors of breast cancer resistance protein ABCG2.

6-Prenylchrysin and tectochrysin constitute new and promising inhibitors for the reversal of ABCG2-mediated drug transport.

Effect of Breast Cancer Resistance Protein (Bcrp/Abcg2) on the Disposition of Phytoestrogens

The results suggest that Bcrp limits the oral availability and distribution into the brain and testis, epididymis, and fetus of phytoestrogens.

Effect of Organic Isothiocyanates on Breast Cancer Resistance Protein (ABCG2)-Mediated Transport

ITCs significantly increased MX accumulation and reversed its cytotoxicity in resistant cells, but had a small or no effect in sensitive cells, and certain ITCs are BCRP inhibitors and PEITC and/or its cellular metabolite(s) may represent B CRP substrates, suggesting the potential for diet-drug interactions.
...