RRC ID 78304
Author Nakamura T, Oka M, Aizawa K, Soda H, Fukuda M, Terashi K, Ikeda K, Mizuta Y, Noguchi Y, Kimura Y, Tsuruo T, Kohno S.
Title Direct interaction between a quinoline derivative, MS-209, and multidrug resistance protein (MRP) in human gastric cancer cells.
Journal Biochem Biophys Res Commun
Abstract MS-209 is a novel quinoline derivative reversing P-glycoprotein-mediated multidrug resistance (MDR). We investigated the interaction between MS-209 and multidrug resistance protein (MRP) in MRP-overexpressing human gastric cancer cells. We measured [3H]leukotriene C4 uptake into the membrane vesicles of the cells and intracellular calcein and [3H]vincristine accumulation with or without MS-209. In multi-drug-resistant MKN45R0.8 cells selected by doxorubicin, MS-209 dose dependently reduced MRP-mediated [3H]leukotriene C4 uptake and increased calcein accumulation. In both resistant and unselected cell lines expressing the MRP gene, MS-209 increased [3H]vincristine accumulation in proportion with the level of MRP mRNA expression and enhanced the cytotoxicity of etoposide, doxorubicin, and vincristine. The reversal effects correlated with the level of MRP mRNA expression in these cells. Our results indicate that MS-209 effectively reverses intrinsic and acquired MRP-mediated MDR of gastric cancer cells by interacting directly with MRP.
Volume 255(3)
Pages 618-24
Published 1999-2-24
DOI 10.1006/bbrc.1999.0245
PII S0006-291X(99)90245-0
PMID 10049760
MeSH ATP-Binding Cassette Transporters / genetics ATP-Binding Cassette Transporters / metabolism* Antineoplastic Agents / metabolism Doxorubicin / metabolism Drug Resistance, Multiple / genetics Etoposide / metabolism Fluoresceins / metabolism Gene Expression Regulation, Neoplastic / genetics Genes, MDR / genetics Humans Leukotriene C4 / pharmacokinetics Multidrug Resistance-Associated Proteins Neoplasm Proteins / metabolism Probenecid / pharmacology Quinolines / metabolism* Quinolines / pharmacology RNA, Messenger / genetics Stomach Neoplasms / metabolism* Tumor Cells, Cultured Vincristine / metabolism
IF 2.985
Resource
Human and Animal Cells MKN45(RCB1001)