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 Drugsjournal_title
Anti-cancer drugsauthors
Engman L,McNaughton M,Gajewska M,Kumar S,Birmingham A,Powis Gdoi
10.1097/00001813-200606000-00007subject
Has Abstractpub_date
2006-06-01 00:00:00pages
539-44issue
5eissn
0959-4973issn
1473-5741pii
00001813-200606000-00007journal_volume
17pub_type
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