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A novel platinum compound inhibits telomerase activity in vitro and reduces telomere length in a human hepatoma cell line
Author(s) -
Furuta Miho,
Nozawa Katsura,
Takemura Masaharu,
Izuta Shunji,
Murate Takashi,
Tsuchiya Masayuki,
Yoshida Kenji,
Taka Naoki,
Nimura Yuji,
Yoshida Shonen
Publication year - 2003
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.11022
Subject(s) - telomerase , telomere , cisplatin , in vitro , growth inhibition , primer (cosmetics) , microbiology and biotechnology , chemistry , cell culture , platinum , biology , biochemistry , dna , chemotherapy , genetics , organic chemistry , gene , catalysis
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.