Thioredoxin reductase and cancer cell growth inhibition by organogold(III) compounds.

Abstract:

:Thioredoxin (Trx) expression is increased in several human primary cancers associated with aggressive tumor growth and decreased patient survival, and the Trx/Trx reductase (TrxR) system therefore provides an attractive target for cancer drug development. Various gold(III) compounds with none, one, two or three carbon-gold bonds were evaluated for their capacity to inhibit TrxR and the growth of MCF-7 cancer cells in vitro. Compounds with up to two carbon-gold bonds were often potent inhibitors of TrxR with IC50 values as low as 2 nmol/l. In the presence of Trx and insulin the inhibiting capacity was much lower. However, the inhibitory concentrations of the compounds did not correlate with the ability to kill cells. Out of the organometallics tested, only compound 8 with two carbon-gold bonds was able to inhibit colony formation by MCF-7 breast cancer cells at low micromolar concentrations (IC50=1.6 micromol/l). Unfortunately, the compound did not show any anti-tumor activity against MCF-7 breast cancer and HT-29 colon cancer xenografts in scid mice.

journal_name

Anticancer Drugs

journal_title

Anti-cancer drugs

authors

Engman L,McNaughton M,Gajewska M,Kumar S,Birmingham A,Powis G

doi

10.1097/00001813-200606000-00007

subject

Has Abstract

pub_date

2006-06-01 00:00:00

pages

539-44

issue

5

eissn

0959-4973

issn

1473-5741

pii

00001813-200606000-00007

journal_volume

17

pub_type

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