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Utilizing Murine Inducible Telomerase Alleles in the Studies of Tissue Degeneration/Regeneration and Cancer
08:34

Utilizing Murine Inducible Telomerase Alleles in the Studies of Tissue Degeneration/Regeneration and Cancer

Published on: April 13, 2015

Telomerase activity and telomere length in human tumor cells with acquired resistance to anticancer agents

V Smith1, F Dai, M Spitz

  • 1Institute for Experimental Oncology, Oncotest GmbH, Freiburg, Germany.

Journal of Chemotherapy (Florence, Italy)
|November 26, 2009
PubMed

Insights

Standard chemotherapy agents can influence cancer drug resistance by affecting telomere length and telomerase activity. These telomere maintenance mechanisms are crucial for overcoming resistance and optimizing telomere-based cancer therapeutics.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Telomeres and telomerase are key targets in anticancer drug development.
  • Cytotoxic agents may influence cancer drug resistance by affecting telomere length and telomerase activity.

Purpose of the Study:

  • To investigate the role of telomere length and telomerase activity in acquired resistance to chemotherapy.
  • To assess drug efflux pump expression, glutathione (GSH) levels, and polyadenosine-ribose polymerase (PARP) cleavage in drug-resistant cancer cell lines.

Main Methods:

  • Human tumor cell lines resistant to vindesine, gemcitabine, and cisplatin were generated.
  • Telomere lengths, telomerase activity, drug efflux pump expression, GSH levels, and PARP cleavage were assessed.
  • Resistant clones were compared to parental lines and evaluated for cross-resistance.

Main Results:

  • Drug resistance mechanisms were not linked to drug efflux pump expression, GSH levels, or PARP cleavage.
  • All resistant cell lines exhibited alterations in telomerase activity and/or telomere length.
  • Complex cross-resistance patterns were observed, but not directly correlated with the assessed molecular markers.

Conclusions:

  • Telomere maintenance plays a significant role in cancer drug resistance.
  • Strategies to overcome drug resistance should consider telomere dynamics.
  • Telomere maintenance mechanisms are important for optimizing telomere-based cancer therapeutics.

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