کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1950659 1537957 2012 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Telomerase antagonist imetelstat inhibits esophageal cancer cell growth and increases radiation-induced DNA breaks
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Telomerase antagonist imetelstat inhibits esophageal cancer cell growth and increases radiation-induced DNA breaks
چکیده انگلیسی

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 γ-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.


► Imetelstat inhibits telomerase activity in esophageal cancer cells.
► Imetelstat decreases cell proliferation and colony formation ability.
► Imetelstat increases the number and size of radiation induced DNA breaks.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research - Volume 1823, Issue 12, December 2012, Pages 2130–2135
نویسندگان
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