Next Article in Journal
CRMP2 as a Candidate Target to Interfere with Lung Cancer Cell Migration
Previous Article in Journal
Decoding Stem Cells: An Overview on Planarian Stem Cell Heterogeneity and Lineage Progression
 
 
Article

Reversal of ABCG2/BCRP-Mediated Multidrug Resistance by 5,3′,5′-Trihydroxy-3,6,7,4′-Tetramethoxyflavone Isolated from the Australian Desert Plant Eremophila galeata Chinnock

1
Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark
2
Centre de Biochimie Structurale (CBS), INSERM, CNRS, Université de Montpellier, 29 rue de Navacelles, 34090 Montpellier, France
3
Quality Use of Medicines and Pharmacy Research Centre, Clinical and Health Sciences, University of South Australia, Adelaide, SA 5000, Australia
4
Wise Owl Consulting, Como, WA 6152, Australia
*
Author to whom correspondence should be addressed.
Academic Editor: Vladimir N. Uversky
Biomolecules 2021, 11(10), 1534; https://doi.org/10.3390/biom11101534
Received: 24 March 2021 / Revised: 5 October 2021 / Accepted: 9 October 2021 / Published: 18 October 2021
Multidrug resistance (MDR) is a major challenge in cancer treatment, and the breast cancer resistance protein (BCRP) is an important target in the search for new MDR-reversing drugs. With the aim of discovering new potential BCRP inhibitors, the crude extract of leaves of Eremophila galeata, a plant endemic to Australia, was investigated for inhibitory activity of parental (HT29par) as well as BCRP-overexpressing HT29 colon cancer cells resistant to the chemotherapeutic SN-38 (i.e., HT29SN38 cells). This identified a fraction, eluted with 40% acetonitrile on a solid-phase extraction column, which showed weak growth-inhibitory activity on HT29SN38 cells when administered alone, but exhibited concentration-dependent growth inhibition when administered in combination with SN-38. The major constituent in this fraction was isolated and found to be 5,3′,5′-trihydroxy-3,6,7,4′-tetramethoxyflavone (2), which at a concentration of 25 μg/mL potentiated the growth-inhibitory activity of SN-38 to a degree comparable to that of the known BCRP inhibitor Ko143 at 1 μM. A dye accumulation experiment suggested that 2 inhibits BCRP, and docking studies showed that 2 binds to the same BCRP site as SN-38. These results indicate that 2 acts synergistically with SN-38, with 2 being a BCRP efflux pump inhibitor while SN-38 inhibits topoisomerase-1. View Full-Text
Keywords: Eremophila galeata; breast cancer resistance protein; multidrug resistance; docking Eremophila galeata; breast cancer resistance protein; multidrug resistance; docking
Show Figures

Figure 1

MDPI and ACS Style

Petersen, M.J.; Lund, X.L.; Semple, S.J.; Buirchell, B.; Franzyk, H.; Gajhede, M.; Kongstad, K.T.; Stenvang, J.; Staerk, D. Reversal of ABCG2/BCRP-Mediated Multidrug Resistance by 5,3′,5′-Trihydroxy-3,6,7,4′-Tetramethoxyflavone Isolated from the Australian Desert Plant Eremophila galeata Chinnock. Biomolecules 2021, 11, 1534. https://doi.org/10.3390/biom11101534

AMA Style

Petersen MJ, Lund XL, Semple SJ, Buirchell B, Franzyk H, Gajhede M, Kongstad KT, Stenvang J, Staerk D. Reversal of ABCG2/BCRP-Mediated Multidrug Resistance by 5,3′,5′-Trihydroxy-3,6,7,4′-Tetramethoxyflavone Isolated from the Australian Desert Plant Eremophila galeata Chinnock. Biomolecules. 2021; 11(10):1534. https://doi.org/10.3390/biom11101534

Chicago/Turabian Style

Petersen, Malene J., Xamuel L. Lund, Susan J. Semple, Bevan Buirchell, Henrik Franzyk, Michael Gajhede, Kenneth T. Kongstad, Jan Stenvang, and Dan Staerk. 2021. "Reversal of ABCG2/BCRP-Mediated Multidrug Resistance by 5,3′,5′-Trihydroxy-3,6,7,4′-Tetramethoxyflavone Isolated from the Australian Desert Plant Eremophila galeata Chinnock" Biomolecules 11, no. 10: 1534. https://doi.org/10.3390/biom11101534

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop