A novel platinum compound inhibits telomerase activity in vitro and reduces telomere length in a human hepatoma cell line

✍ Scribed by Miho Furuta; Katsura Nozawa; Masaharu Takemura; Shunji Izuta; Takashi Murate; Masayuki Tsuchiya; Kenji Yoshida; Naoki Taka; Yuji Nimura; Shonen Yoshida

• Publisher: John Wiley and Sons
• Year: 2003
• Tongue: French
• Weight: 275 KB
• Volume: 104
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.11022

✦ Synopsis

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.