Active transport of glutathione S-conjugate in human colon adenocarcinoma cells

被引:13
|
作者
Zhang, K [1 ]
Wong, KP [1 ]
机构
[1] NATL UNIV SINGAPORE,FAC MED,DEPT BIOCHEM,SINGAPORE 119260,SINGAPORE
关键词
glutathione S-conjugate pump; human colon cancer cells; monochlorobimane; chlorambucil; glutathione S-transferase;
D O I
10.1016/S0304-3835(96)04457-6
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The formation of the glutathione S-conjugate of monochlorobimane (GSH-bimane) in human colon adenocarcinoma cells was identified by HPLC-fluorimetry and its transport from the cells was found to be temperature-sensitive, saturable and ATP-dependent. The apparent K-m and V-max values were 2.4 +/- 0.5 nmol GSH-bimane/10(6) cells and 0.5 +/- 0.1 nmol GSH-bimane/min per 10(6) cells, respectively. This active transport of GSH-bimane was inhibited by low micromolar concentrations of classical uncouplers of oxidative phosphorylation, namely carbonylcyanide p-trifluoromethoxyphenylhydrazone (FCCP), carbonylcyanide m-chlorophenylhydrazone (CCCP) and 2,4-dinitrophenol (DNP). The efflux of GSH-bimane was competitively inhibited by chlorambucil (CMB) and 1-chloro-2,4-dinitrobenzene (CDNB), two other substrates of GST. This study demonstrates the presence and kinetic measurements of the glutathione S-conjugate export (GS-X) pump in human colon cancer cells, an export pump whose function has been implicated in the phenomenon of multidrug resistance.
引用
收藏
页码:143 / 151
页数:9
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