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Joseph P , Sharma MC , Jaiswal AK
Inhibition of Nad(P)H-Quinone Oxidoreductase(1) in Ethacrynic Acid-Resistant Human Colon-Carcinoma Cells
Biochemical Pharmacology. 1994 Jun 1;47(11) :2011-2015
AbstractHuman colon carcinoma HT29 cells sensitive (WT) and resistant (HT/M and HT/S) to ethacrynic acid (EA) were used to investigate the role of NAD(P)H: quinone oxidoreductase(1) (NQO(1)) in drug resistance. Significant decreases in the levels of NQO(1) activity were observed in resistant cells as compared with the sensitive cells. However, the decreased activities of NQO(1) in resistant cells were found to be due to inhibition of the enzyme by EA. Human NQO(1) cDNA-derived protein in monkey kidney COS1 cell extract was used to demonstrate that in vitro inhibition of NQO(1) activity by EA was rapid, reversible and concentration dependent, with an IC50 value of 250 mu M. These results suggest that NQO(1) may not have a role in EA resistance of human colon carcinoma HT29 cells and that EA is an inhibitor of NQO(1) activity.
NotesEnglish Article NR730 BIOCHEM PHARMACOL