Understanding dihydro-ß-agarofuran sesquiterpenes from Tripterygium hypoglaucum as the modulators of multi-drug resistance in HepG2/Adr cells.
Biochem Biophys Res Commun
; 508(3): 742-748, 2019 01 15.
Article
em En
| MEDLINE
| ID: mdl-30528235
ABSTRACT
Multi-drug resistance (MDR) is one of the dominant reasons for the failure of cancer chemotherapy. P-glycoprotein (P-gp) over-expression in the plasma membrane of drug-resistant tumor cells promotes the efflux of chemotherapeutic agents and plays a significant role in MDR. Several investigations have suggested that dihydro-ß-agarofuran sesquiterpenes are the potential modulators of MDR. However, their cellular mechanism in regulating P-gp has not been fully explored. Seven dihydro-ß-agarofuran sesquiterpenes (1-7) from Tripterygium hypoglaucum was evaluated for the chemoreversal activity of HepG2/Adr cells. 1, 2, 4, 5, and 7 were active with reversal fold ranging from 47.68 to 456.90. The image-based high-screening indicated that all of the active compounds were capable of decreasing the efflux of doxorubicin (Dox). The most potent 4 did not affect the expression or subcellular distribution of P-gp. P-gp ATPase activity was stimulated by 4 in a dose-depend manner, suggesting that 4 may be the substrate of P-gp. The docking data implied that 4 took PHE 979, PHE 332, and GLN 986 to bind with P-gp. Taken together, the results demonstrated that dihydro-ß-agarofuran sesquiterpenes from T. Hypoglaucum were the substrate of P-gp and potential modulators of MDR.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sesquiterpenos
/
Doxorrubicina
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Resistência a Múltiplos Medicamentos
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Resistencia a Medicamentos Antineoplásicos
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Tripterygium
Limite:
Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
China