Inhibition of P‐Glycoprotein‐Induced Multidrug Resistance by a Clerodane‐Type Diterpenoid from Sindora sumatrana |
| |
Authors: | Joo‐Won Nam Song?Wha Chae Yoo‐Jin Lee Eun‐Kyoung Seo Hwa?Jeong Lee |
| |
Institution: | 1. Division of Life and Pharmaceutical Sciences and College of Pharmacy, Ewha Womans University, 11‐1 Daehyun‐dong, Seodaemun‐gu, Seoul 120‐750, Korea, (phone: +82‐2‐3277‐3047 (E.‐K.?S.), +82‐2‐3277‐3409 (H.?J.?L.);2. (E.‐K.?S.), (H.?J.?L.)) |
| |
Abstract: | The aim of the present study was to investigate the effects of di‐ and sesquiterpenoids isolated from the pods of Sindora sumatrana Miq. (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. |
| |
Keywords: | Sindora sumatrana Multidrug resistance P‐Glycoprotein inhibitors Sesquiterpenoids Clerodane‐type diterpenoids |
|
|