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Benzo[b]thiophenesulphonamide 1,1-dioxide derivatives inhibit tNOX activity in a redox state-dependent manner.

Abstract：

:Benzo[b]thiophenesulphonamide 1,1-dioxide (BTS) derivatives are strong cytotoxic agents that induce reactive oxygen species (ROS) overproduction and apoptosis in tumour cells. Although the precise origin of BTS-induced ROS is not known, a clear correlation between their cytotoxic effect and ability to inhibit a tumour-associated NADH oxidase (tNOX) activity of the plasma membrane has been described. To analyse the putative implication of tNOX in BTS-induced ROS generation, in this work we have synthesised and tested a new BTS derivative, the 6-[N-(2-phenylethyl)]benzo[b]thiophenesulphonamide 1,1-dioxide. According to its high lipophilicity, this compound showed a strong cytotoxic activity against a panel of six human tumour cell lines, including two human leukaemia (K-562 and CCRF-CEM) and four human solid tumours (HT-29, HTB54, HeLa and MEL-AC). We also tested the ability of this compound to inhibit the tNOX activity and we found an absolute dependence of this inhibition on the redox state of the tNOX: while under reducing conditions, that is, 100 mM GSH, the drug inhibits strongly the NOX activity with an EC(50) of about 0.1 nM, under oxidising conditions, there is no effect of the drug or just a slight stimulation of activity.

journal_name

Br J Cancer

journal_title

British journal of cancer

authors

Encío I,Morré DJ,Villar R,Gil MJ,Martínez-Merino V

doi

10.1038/sj.bjc.6602383

subject

Has Abstract

pub_date

2005-02-28 00:00:00

pages

690-5

issue

4

eissn

0007-0920

issn

1532-1827

pii

6602383

journal_volume

92

pub_type

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