Telomerase antagonist imetelstat inhibits esophageal cancer cell growth and increases radiation-induced DNA breaks
2012 (English)In: Biochimica et Biophysica Acta. Molecular Cell Research, ISSN 0167-4889, Vol. 1823, no 12, 2130-2135 p.Article in journal (Refereed) Published
Telomerase is mainly active in human tumor cells, which provides an opportunity for a therapeutic window on telomerase targeting. We sought to evaluate the potential of the thio-phosphoramidate oligonucleotide inhibitor of telomerase, imetelstat, as a drug candidate for treatment of esophageal cancer. Our results showed that imetelstat inhibited telomerase activity in a dose-dependent manner in esophageal cancer cells. After only 1 week of imetelstat treatment, a reduction of colony formation ability of esophageal cancer cells was observed. Furthermore, long-term treatment with imetelstat decreased cell growth of esophageal cancer cells with different kinetics regarding telomere lengths. Short-term imetelstat treatment also increased gamma-H2AX and 53BP1 foci staining in the esophageal cancer cell lines indicating a possible induction of DNA double strand breaks (DSBs). We also found that pre-treatment with imetelstat led to increased number and size of 53BP1 foci after ionizing radiation. The increase of 53BP1 foci number was especially pronounced during the first 1 h of repair whereas the increase of foci size was prominent later on. This study supports the potential of imetelstat as a therapeutic agent for the treatment of esophageal cancer.
Place, publisher, year, edition, pages
Elsevier, 2012. Vol. 1823, no 12, 2130-2135 p.
Telomerase, Esophageal cancer, Imetelstat, DNA double strand break, gamma-H2AX and 53BP1 foci
Cancer and Oncology
IdentifiersURN: urn:nbn:se:umu:diva-64453DOI: 10.1016/j.bbamcr.2012.08.003ISI: 000312629200004OAI: oai:DiVA.org:umu-64453DiVA: diva2:603274