Telomerase Inhibition Combined with Other Chemotherapeutic Reagents to Enhance Anti-Cancer Effect

  • Tetsuzo Tauchi
  • Junko H. Ohyashiki
  • Kazuma Ohyashiki
Part of the Methods in Molecular Biology™ book series (MIMB, volume 405)

Summary

Genetic experiments using a dominant-negative form of human telomerase (DN-hTERT) demonstrated that telomerase inhibition can result in telomeric shortening followed by proliferation arrest and cell death by apoptosis. Neoplastic cells from telomerase RNA null (mTERC−/−) mice showed enhanced chemosensitivity to doxorubicin or related double-strand DNA break (DSB)-inducing agents. Telomerase dysfunction, rather than telomerase inhibition, is proposed to be the principal determinant governing chemosensitivity specifically to DSB-inducing agents. We observed that imatinib and vincristine (VCR), in addition to DSB-inducing agents, also enhanced chemosensitivity in telomestatin-treated K562 cells. This observation suggests that combined use of telomerase inhibitors and imatinib or other chemotherapeutic agents may be a very useful approach to treatment of BCR-ABL-positive leukemia.

Key Words

Telomerase inhibition G-quadruplex apoptosis hTERT 

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Copyright information

© Springer 2007

Authors and Affiliations

  • Tetsuzo Tauchi
    • 1
  • Junko H. Ohyashiki
    • 1
  • Kazuma Ohyashiki
    • 1
  1. 1.First Department of Internal MedicineTokyo Medical UniversityTokyoJapan

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