title: Inhibition of P-glycoprotein-induced multidrug resistance by a clerodane-type diterpenoid from Sindora sumatrana.
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, (+)-7beta-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 IC(50) 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.
authors: Division of Life and Pharmaceutical Sciences and College of Pharmacy, Ewha Womans University, 11-1 Daehyun-dong, Seodaemun-gu, Seoul 120-750, Korea.
authors: Ho Jin
authors: HJ
authors: Jung
authors: Soo Yeon
authors: SY
authors: Chung
authors: Joo-Won
authors: JW
authors: Nam
authors: Song Wha
authors: SW
authors: Chae
authors: Yoo-Jin
authors: YJ
authors: Lee
authors: Eun-Kyoung
authors: EK
authors: Seo
authors: Hwa Jeong
authors: HJ
authors: Lee
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors*; D001943:Breast Neoplasms / Q000188:drug therapy; D045744:Cell Line, Tumor; D004224:Diterpenes / Q000737:chemistry / Q000494:pharmacology*; D045785:Diterpenes, Clerodane / Q000737:chemistry / Q000494:pharmacology*; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D007887:Fabaceae / Q000737:chemistry*; D005260:Female; D006801:Humans; D015394:Molecular Structure
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004224:Diterpenes; D045785:Diterpenes, Clerodane