In:
International Journal of Cancer, Wiley, Vol. 104, No. 6 ( 2003-05-10), p. 709-715
Abstract:
Telomerase activity is detectable in most human tumors but not in most normal somatic cells or tissues. Telomerase inhibition has, therefore, been proposed as a novel and potentially selective strategy for antitumor therapy. In the present study, we found that platinum compounds, including cisplatin [cis‐diamminedichloro‐platinum (II)], strongly inhibited the activity of partially purified rat telomerase. Among the agents tested, 2,3‐dibromosuccinato [2‐(methylaminomethyl)pyridine] platinum (II) (compound E) exhibited the strongest inhibition, with an median inhibitory concentration (IC 50 ) of 0.8 μM. The mode of inhibition was noncompetitive with either dNTPs or TS (first) primer, with K i values estimated to be 2.3 or 3.9 μM for varied TS primer or dNTPs, respectively. Notably, cisplatin also inhibited the telomerase activity, with an IC 50 of 2.0 μM. Again, the mode of inhibition was noncompetitive, with K i values estimated as 7.3 or 8.1 μM. Preincubation of TS primer with compound E did not affect the telomerase inhibition, whereas preincubation with cisplatin caused remarkable enhancement. Treatment of a human hepatoma cell line HepG2 with a low concentration of compound E gradually reduced the telomere length, indicating that this compound was able to inhibit telomerase in living cells as well as in vitro . © 2003 Wiley‐Liss, Inc.
Type of Medium:
Online Resource
ISSN:
0020-7136
,
1097-0215
Language:
English
Publisher:
Wiley
Publication Date:
2003
detail.hit.zdb_id:
218257-9
detail.hit.zdb_id:
1474822-8
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