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Inhibition of P-glycoprotein-induced multidrug resistance by a clerodane-type diterpenoid from Sindora sumatrana
- Inhibition of P-glycoprotein-induced multidrug resistance by a clerodane-type diterpenoid from Sindora sumatrana
- Jung H.J.; Chung S.Y.; Nam J.-W.; Chae S.W.; Lee Y.-J.; Seo E.-K.; Lee H.J.
- Ewha Authors
- 서은경; 이화정
- SCOPUS Author ID
- 서은경; 이화정
- Issue Date
- Journal Title
- Chemistry and Biodiversity
- vol. 7, no. 8, pp. 2095 - 2101
- SCIE; SCOPUS
- 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.
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