TY - JOUR AU - Michaelis, Martin AU - Rothweiler, Florian AU - Nerreter, Thomas AU - Sharifi, Mohsen AU - Ghafourian, Taravat AU - Cinatl, Jindrich PY - 2014/03/10 Y2 - 2024/03/28 TI - Karanjin interferes with ABCB1, ABCC1, and ABCG2 JF - Journal of Pharmacy & Pharmaceutical Sciences JA - J Pharm Pharm Sci VL - 17 IS - 1 SE - Pharmaceutical Sciences; Review Articles DO - 10.18433/J3BW2S UR - https://journals.library.ualberta.ca/jpps/index.php/JPPS/article/view/20635 SP - 92-105 AB - <p>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-3<sup>ABCB1</sup>, UKF-NB-3<sup>r</sup>VCR<sup>10</sup>; ABCC1: G62, PC-3<sup>r</sup>VCR<sup>20</sup>; ABCG2: UKF-NB-3<sup>ABCG2</sup>) 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.</p><p><strong> </strong></p><p>This article is open to <strong>POST-PUBLICATION REVIEW</strong>. Registered readers (see “For Readers”) may <strong>comment</strong> by clicking on ABSTRACT on the issue’s contents page.</p><p>METHODS: Cells expressing the relevant transporters (ABCB1: UKF-NB-3<sup>ABCB1</sup>, UKF-NB-3<sup>r</sup>VCR<sup>10</sup>; ABCC1: G62, PC-3<sup>r</sup>VCR<sup>20</sup>; ABCG2: UKF-NB-3<sup>ABCG2</sup>) 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.</p><p>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.</p>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. ER -