TY - JOUR
T1 - Inhibition of P-glycoprotein-induced multidrug resistance by a clerodane-type diterpenoid from Sindora sumatrana
AU - Jung, Ho Jin
AU - Chung, Soo Yeon
AU - Nam, Joo Won
AU - Chae, Song Wha
AU - Lee, Yoo Jin
AU - Seo, Eun Kyoung
AU - Lee, Hwa Jeong
PY - 2010/8
Y1 - 2010/8
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=77956207552&partnerID=8YFLogxK
U2 - 10.1002/cbdv.201000010
DO - 10.1002/cbdv.201000010
M3 - Article
C2 - 20730973
AN - SCOPUS:77956207552
SN - 1612-1872
VL - 7
SP - 2095
EP - 2101
JO - Chemistry and Biodiversity
JF - Chemistry and Biodiversity
IS - 8
ER -
