Pharmacological telomerase inhibition can sensitize drug-resistant and drug-sensitive cells to chemotherapeutic treatment

Telomerase is the ribonucleoprotein enzyme whose principal function is to catalyze the de novo addition of telomeric repeats to the ends of linear chromosomes. Telomerase activity is predominantly observed in cancerous tissues and rarely in normal somatic cells making telomerase an attractive anticancer target. BIBR1532 is a highly selective pharmacological inhibitor of telomerase catalytic activity and induces telomere shortening and eventual growth arrest. We treated drug-sensitive and drug-resistant human leukemia and breast cancer cells lines with BIBR1532 and observed telomere shortening and a progressive decrease in proliferative capacity or colony forming ability. This effect was increased with the co-treatment of traditional chemotherapeutics, suggesting that pharmacological telomerase inhibition in combination with chemotherapeutics may be a valid strategy for the treatment of both drug-resistant and drug-sensitive cancers. Finally, our results support further investigation and development of pharmacological inhibitors of telomerase catalytic activity