Second-generation tyrosine kinase inhibitors reduce telomerase activity in K562 cells

Saar Shapira, Galit Granot, Rahav Mor-Tzuntz, Pia Raanani, Orit Uziel, Meir Lahav, Ofer Shpilberg

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


In this study we present the effects of nilotinib and dasatinib on telomerase activity and regulation. Nilotinib and dasatinib strongly reduced telomerase activity in BCR-ABL-positive (K562) and BCR-ABL-negative (HL60) cells, demonstrating that their effect on telomerase activity is uncoupled from their effect on BCR-ABL. Nilotinib and dasatinib caused a substantial decrease in hTERT mRNA expression. Phospho-Sp1 regulates hTERT transcription. We detected a considerable decrease in Sp1 nuclear expression and binding to the hTERT promoter following exposure to the drugs. We also detected a reduction in Map kinase, known to phosphorylate Sp1. Telomerase is also activated and translocated to the nucleus when phosphorylated by AKT. We detected a decrease in phospho-AKT and a reduction in the nuclear expression of hTERT following exposure to nilotinib and dasatinib.In conclusion, we provide evidence for transcriptional and post-translational inhibition of telomerase by nilotinib and dasatinib which is not necessarily mediated via known targets of these tyrosine kinase inhibitors.

Original languageEnglish
Pages (from-to)223-231
Number of pages9
JournalCancer Letters
Issue number2
StatePublished - 28 Oct 2012
Externally publishedYes


  • CML
  • Dasatinib
  • Nilotinib
  • Sp1
  • Telomerase

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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