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Eur J Pharmacol. 2014 Jan 15;723:346-52. doi: 10.1016/j.ejphar.2013.11.005. Epub 2013 Nov 20.

Dietary polyacetylenes of the falcarinol type are inhibitors of breast cancer resistance protein (BCRP/ABCG2).

Author information

1
Food Innovation, The New Zealand Institute for Plant & Food Research Limited, Private Bag 92169, Auckland, New Zealand; School of Biological Sciences, Faculty of Science, The University of Auckland, Auckland, New Zealand; Department of Pharmacology and Clinical Pharmacology, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand. Electronic address: kee.tan@plantandfood.co.nz.
2
Department of Chemistry, University of Otago, Dunedin, New Zealand.
3
School of Interprofessional Health Studies, Faculty of Health and Environmental Sciences, Auckland University of Technology, Auckland, New Zealand.
4
Department of Pharmacology and Clinical Pharmacology, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand.
5
School of Biological Sciences, Faculty of Science, The University of Auckland, Auckland, New Zealand; Centre for Brain Research, The University of Auckland, Auckland, New Zealand.
6
Food Innovation, The New Zealand Institute for Plant & Food Research Limited, Private Bag 92169, Auckland, New Zealand.

Abstract

Polyacetylenes of the falcarinol type are present in vegetables such as carrots and parsley. They display interesting bioactivities and hold potential as health-promoting and therapeutic agents. In this study, falcarinol, falcarindiol, falcarindiol 3-acetate and falcarindiol 3,8-diacetate were examined for their modulation on breast cancer resistance protein (BCRP/ABCG2), an efflux transporter important for xenobiotic absorption and disposition, and multidrug resistance in cancer. Falcarinol, falcarindiol, and falcarindiol 3-acetate were extracted from carrots and falcarindiol 3,8-diacetate prepared from falcarindiol. Their modulatory effects on ABCG2 were studied using three methods-mitoxantrone accumulation, vesicular transport, and ATPase assay. The polyacetylenes inhibited mitoxantrone (an ABCG2 substrate) efflux in ABCG2-overexpressing HEK293 cells. The inhibitory effect was confirmed in the vesicular transport assay, in which concentration-dependent inhibition of methotrexate (an ABCG2 substrate) uptake into ABCG2-overexpressing Sf9 membrane vesicles was observed (IC50=19.7-41.7µM). The polyacetylenes also inhibited baseline and sulfasalazine-stimulated vanadate-sensitive ATPase activities in ABCG2-overexpressing Sf9 membrane vesicles (IC50=19.3-79.3µM). This is the first report of an inhibitory effect of polyacetylenes on ABCG2. These results indicate a prospective use of polyacetylenes as multidrug resistance reversal agents, a possible role of ABCG2 in the absorption and disposition of polyacetylenes, and potential food-drug interactions between polyacetylene-rich foods and ABCG2 substrate drugs.

KEYWORDS:

ABC transporter; BCRP; Falcarindiol; Falcarindiol 3,8-diacetate; Falcarindiol 3-acetate; Falcarinol

PMID:
24269959
DOI:
10.1016/j.ejphar.2013.11.005
[Indexed for MEDLINE]

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