Characterization of 3-methoxy flavones for their interaction with ABCG2 as suggested by ATPase activity

Show simple item record Gallus, Jennifer Juvale, Kapil Wiese, Michael 2014-10-20T18:02:10Z 2014-10-20T18:02:10Z 2014-11
dc.identifier.citation Gallus, Jennifer; Juvale, Kapil and Wiese, Michael, "Characterization of 3-methoxy flavones for their interaction with ABCG2 as suggested by ATPase activity", Biochimica et Biophysica Acta (BBA) - Biomembranes, DOI: 10.1016/j.bbamem.2014.08.003, vol. 1838, no. 11, pp. 2929-2938, Nov. 2014. en_US
dc.identifier.issn 0006-3002
dc.description.abstract Breast Cancer Resistance Protein (BCRP/ABCG2) belongs to the superfamily of ATP binding cassette (ABC) transporters. Characteristic of some of these transporter proteins is the transport of a variety of structurally unrelated substances against a concentration gradient by using the energy of ATP hydrolysis. ABCG2 has been found to confer multidrug resistance (MDR) in cancer cells. Several anticancer drugs have been identified as ABCG2 substrates including mitoxantrone, etoposide and topotecan. As inhibition of the transporter is one of the strategies to overcome MDR, we have synthesized and tested several 3-methoxy flavones and investigated them for their ABCG2 inhibition. Among these, pentamethyl quercetin (compound 4) and pentamethyl morin (compound 5) were found to be fluorescent and hence screened for their possible transport by ABCG2 using confocal microscopy. This study showed that pentamethyl quercetin was far less accumulated in ABCG2 overexpressing MDCK BCRP cells as compared to MDCK sensitive cells, suggesting possible efflux of this compound by ABCG2. Pentamethyl morin showed no visible difference in both cell lines. Based on this observation, we studied several other fluorescent 3-methoxy flavones for their accumulation in ABCG2 overexpressing cells. To confirm the substrate or inhibitor nature of the tested compounds, these compounds were further investigated by ATPase assay. If stimulation of the transporter ATPase activity is detected, one can conclude that the compound is probably a transported substrate. All compounds except pentamethyl morin (compound 5) and tetramethyl quercetin (compound 6) were found to stimulate ATPase activity pointing to possible substrates despite being potent inhibitors of ABCG2. en_US
dc.description.statementofresponsibility by Jennifer Gallus, Kapil Juvale and Michael Wiese
dc.format.extent Vol. 1838, No. 11, pp. 2929-2938
dc.language.iso en en_US
dc.publisher Elsevier en_US
dc.subject ABCG2 en_US
dc.subject BCRP en_US
dc.subject Flavonoids en_US
dc.subject Substrate en_US
dc.subject ATPase en_US
dc.title Characterization of 3-methoxy flavones for their interaction with ABCG2 as suggested by ATPase activity en_US
dc.type Article en_US
dc.relation.journal Biochimica et Biophysica Acta (BBA) - Biomembranes

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