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Karanjin interferes with ABCB1, ABCC1, and ABCG2
journal contribution
posted on 2023-06-09, 03:25 authored by Martin Michaelis, Florian Rothweiler, Thomas Nerreter, Mohsen Sharifi, Taravat Ghafourian, Jindrich Cinatl Jr.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.
History
Publication status
- Published
File Version
- Published version
Journal
Journal of Pharmacy and Pharmaceutical SciencesISSN
1482-1826Publisher
Canadian Society for Pharmaceutical SciencesIssue
1Volume
17Page range
92-105Department affiliated with
- Biochemistry Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2017-12-01First Open Access (FOA) Date
2017-12-01First Compliant Deposit (FCD) Date
2017-12-01Usage metrics
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No categories selectedKeywords
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 proteinhuman; ABCG2 proteinhuman; adenosine triphosphatase; apigenin; benzopyran derivative; flavanone derivative; genistein; karanjin; multidrug resistance protein; multidrug resistance-associated protein 1; naringenin; tumor proteinarticle; 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 lineAdenosine Triphosphatases; Apigenin; ATP-Binding Cassette Transporters; Benzopyrans; Cell LineTumor; Dose-Response RelationshipDrug; Flavanones; Genistein; Humans; Multidrug Resistance-Associated Proteins; Neoplasm Proteins; P-Glycoproteins
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