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Inhibition of P-glycoprotein-induced multidrug resistance by a clerodane-type diterpenoid from Sindora sumatrana

Title
Inhibition of P-glycoprotein-induced multidrug resistance by a clerodane-type diterpenoid from Sindora sumatrana
Authors
Jung H.J.Chung S.Y.Nam J.-W.Chae S.W.Lee Y.-J.Seo E.-K.Lee H.J.
Ewha Authors
서은경이화정
SCOPUS Author ID
서은경scopus; 이화정scopus
Issue Date
2010
Journal Title
Chemistry and Biodiversity
ISSN
1612-1872JCR Link
Citation
vol. 7, no. 8, pp. 2095 - 2101
Indexed
SCIE; SCOPUS WOS scopus
Abstract
The aim of the present study was to investigate the effects of di- and sesquiterpenoids isolated from the pods of Sindora sumatranaMiq. (Leguminosae) on P-glycoprotein (P-gp) function in an adriamycin-resistant human breast cancer cell line, MCF-7/ADR. Over-expression of P-gp is known to be one of the mechanisms involved in multidrug resistance (MDR), which is a major obstacle in clinical cancer treatment. Among six di- and sesquiterpenoids extracted from S. sumatrana, (+)-7β-acetoxy-15,16-epoxycleroda-3,13(16),14-trien-18-oic acid (1) showed a strong P-gp inhibitory effect, as great as that of verapamil, a representative P-gp inhibitor. Compound 1 enhanced daunomycin accumulation more than fourfold and significantly decreased daunomycin efflux compared with control, resulting in a decrease in the IC50 value for daunomycin. These results suggest that compound 1 inhibits the functioning of P-gp and, therefore, can be developed as an MDR-reversing agent. © 2010 Verlag Helvetica Chimica Acta AG.
DOI
10.1002/cbdv.201000010
Appears in Collections:
약학대학 > 약학과 > Journal papers
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