Karanjin interferes with ABCB1, ABCC1, and ABCG2

Michaelis, Martin, Rothweiler, Florian, Nerreter, Thomas, Sharifi, Mohsen, Ghafourian, Taravat and Cinatl Jr., Jindrich (2014) Karanjin interferes with ABCB1, ABCC1, and ABCG2. Journal of Pharmacy and Pharmaceutical Sciences, 17 (1). pp. 92-105. ISSN 1482-1826

[img] PDF - Published Version
Download (533kB)


PURPOSE: The prominent ATP-binding cassette (ABC) transporters ABCB1, ABCC1, and ABCG2 are involved in substance transport across physiological barriers and therefore in drug absorption, distribution, and elimination. They also mediate multi-drug resistance in cancer cells. Different flavonoids are known to interfere with different ABC transporters. Here, the effect of the furanoflavonol karanjin, a potential drug with antiglycaemic, gastroprotective, antifungal, and antibacterial effects, was investigated on ABCB1, ABCC1, and ABCG2-mediated drug transport in comparison to the flavonoids apigenin, genistein, and naringenin. METHODS: Cells expressing the relevant transporters (ABCB1: UKF-NB-3ABCB1, UKF-NB-3rVCR10; ABCC1: G62, PC-3rVCR20; ABCG2: UKF-NB-3ABCG2) were used in combination with specific fluorescent and cytotoxic ABC transporter substrates and ABC transporter inhibitors to study ABC transporter function. Moreover, the effects of the investigated flavonoids were determined on the ABC transporter ATPase activities. RESULTS: Karanjin interfered with drug efflux mediated by ABCB1, ABCC1, and ABCG2 and enhanced the ATPase activity of all three transporters. Moreover, karanjin exerted more pronounced effects than the control flavonoids apigenin, genistein, and naringenin on all three transporters. Most notably, karanjin interfered with ABCB1 at low concentrations being about 1μM. CONCLUSIONS: Taken together, these findings should be taken into account during further consideration of karanjin as a potential drug for different therapeutic indications. The effects on ABCB1, ABCC1, and ABCG2 may affect the pharmacokinetics of co-administered drugs.

Item Type: Article
Keywords: adenosine triphosphatase; apigenin; breast cancer resistance protein; flavonol derivative; genistein; karanjin; mitoxantrone; multidrug resistance associated protein 1; multidrug resistance protein 1; naringenin; unclassified drug; vincristine; ABC transporter; ABCB1 protein, human; ABCG2 protein, human; adenosine triphosphatase; apigenin; benzopyran derivative; flavanone derivative; genistein; karanjin; multidrug resistance protein; multidrug resistance-associated protein 1; naringenin; tumor protein, article; cancer cell culture; concentration response; controlled study; drug cytotoxicity; drug effect; drug potentiation; drug sensitivity; drug sensitization; drug transport; enzyme activity; human; human cell; IC 50; protein expression; protein function; antagonists and inhibitors; dose response; metabolism; tumor cell line, Adenosine Triphosphatases; Apigenin; ATP-Binding Cassette Transporters; Benzopyrans; Cell Line, Tumor; Dose-Response Relationship, Drug; Flavanones; Genistein; Humans; Multidrug Resistance-Associated Proteins; Neoplasm Proteins; P-Glycoproteins
Schools and Departments: School of Life Sciences > Biochemistry
Depositing User: Taravat Ghafourian
Date Deposited: 01 Dec 2017 08:56
Last Modified: 02 Jul 2019 17:17
URI: http://sro.sussex.ac.uk/id/eprint/64129

View download statistics for this item

📧 Request an update