Consequences of telomerase inhibition by BIBR1532 on proliferation and chemosensitivity of chondrosarcoma cell lines

Cancer Invest. 2008 Jul;26(6):590-6. doi: 10.1080/07357900802072905.

Abstract

Purpose: Human chondrosarcomas are generally resistant to conventional treatments like chemotherapy and radiotherapy. We investigated the effects of BIBR1532, an inhibitor of telomerase on chondrosarcoma cells in vitro.

Methods: Telomerase activity, telomere lengths, growth kinetics and chemosensitivity were analyzed in chondrosarcoma cell lines treated with BIBR1532.

Results: BIBR1532 treatment resulted in telomerase inhibition, decrease of telomere length and reduction of growth capacity of telomerase positive chondrosarcoma cells. Although resistant to cisplatin, telomerase positive cells were sensitive to paclitaxel, which rapidly induced telomere erosion.

Conclusion: Targeting of telomeres might represent a valid strategy for the (re-)sensitization of chemoresistant chondrosarcomas.

MeSH terms

  • Aminobenzoates / pharmacology*
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Cell Survival / drug effects
  • Chondrosarcoma / enzymology*
  • Chondrosarcoma / genetics
  • Chondrosarcoma / pathology
  • Cisplatin / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Resistance, Neoplasm / drug effects*
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Kinetics
  • Naphthalenes / pharmacology*
  • Paclitaxel / pharmacology
  • Telomerase / antagonists & inhibitors*
  • Telomerase / metabolism
  • Telomere / drug effects
  • Telomere / metabolism

Substances

  • Aminobenzoates
  • Antineoplastic Agents
  • BIBR 1532
  • Enzyme Inhibitors
  • Naphthalenes
  • TERT protein, human
  • Telomerase
  • Paclitaxel
  • Cisplatin