Inhibition of telomerase in canine cancer cells following telomestatin treatment.
Telomere shortening in normal somatic cells has been proposed as a major barrier to unlimited cellular proliferation. Telomerase is an enzyme capable of maintaining telomere length, and thus bypassing this barrier. In human beings, telomerase activity is restricted to cancer cells and cells of stem or germ cell lineages. Dogs represent a potentially useful clinical model for the development of telomerase-based therapies because telomerase activity is also restricted to cancer cells and stem cells in this species. We examined the ability of telomestatin to inhibit telomerase activity in telomerase-positive D17 and CMT7 canine cancer cell lines. At a concentration of 2 microM, telomestatin treatment resulted in a decrease in telomerase activity, telomere shortening, growth inhibition and apoptosis in telomerase-positive cancer cells. These effects were not seen in telomerase-negative skin fibroblasts or negative controls. These results confirm that telomestatin specifically inhibits telomerase activity in canine cancer cells and strengthens the usefulness of dogs as a model for testing telomerase-based therapies.
Long
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Institute for Comparative Medicine, University of Glasgow, Faculty of Veterinary Medicine, Glasgow, UK.
Argyle
D J
DJ
Gault
E A
EA
Nasir
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