Suppression of ABCG2 mediated MDR in vitro and in vivo by a novel inhibitor of ABCG2 drug transport.
Pharmacol Res
; 121: 184-193, 2017 Jul.
Article
en En
| MEDLINE
| ID: mdl-28455266
ABSTRACT
Cancer is a disease whose treatment is often limited due to the development of a phenomenon known as multidrug resistance (MDR). There is an immense demand for development of novel agents that can overcome the MDR in cancer. A group of transmembrane proteins called ATP-binding cassette transporters, present ubiquitously in the human body possesses a modular architecture, contributing immensely towards the development of MDR. An analysis of structural congeners among a group of compounds led to the discovery of CCTA-1523 that could selectively reverse ABCG2-mediated MDR in cancer cells in vitro and in vivo. CCTA-1523 (5µM) sensitized the ABCG2 overexpressing cancer cells and ABCG2 transfected cells to the substrate chemotherapeutic drugs. The reversal ability of CCTA-1523 was primarily due to the inhibition of the efflux function of ABCG2; also there was no change in the protein expression or the localization of the ABCG2 in the presence of CCTA-1523. The reversal effect of CCTA-1523 was reversible. Importantly, co-administration of CCTA-1523 restored the in vivo antitumor activity of doxorubicin in ABCG2 overexpressing tumor xenografts. Taken together, our findings indicate that CCTA-1523 is a potent, selective and reversible modulator of ABCG2 that may offer therapeutic promise for multidrug- resistant malignancies.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Resistencia a Múltiples Medicamentos
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Resistencia a Antineoplásicos
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Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2
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Acetanilidas
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Neoplasias
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Antineoplásicos
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Pharmacol Res
Asunto de la revista:
FARMACOLOGIA
Año:
2017
Tipo del documento:
Article
País de afiliación:
Estados Unidos