Karanjin interferes with ABCB1, ABCC1, and ABCG2.
J Pharm Pharm Sci
; 17(1): 92-105, 2014.
Article
em En
| MEDLINE
| ID: mdl-24735762
ABSTRACT
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(ABCB1), UKF-NB-3(r)VCR¹°; ABCC1 G62, PC-3(r)VCR²°; ABCG2 UKF-NB-3(ABCG2)) 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 1 µM.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.
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Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Benzopiranos
/
Transportadores de Cassetes de Ligação de ATP
/
Proteínas Associadas à Resistência a Múltiplos Medicamentos
/
Proteínas de Neoplasias
Limite:
Humans
Idioma:
En
Revista:
J Pharm Pharm Sci
Assunto da revista:
FARMACIA
/
FARMACOLOGIA
Ano de publicação:
2014
Tipo de documento:
Article