Inhibition of telomerase increases the susceptibility of human malignant glioblastoma cells to cisplatin-induced apoptosis.
Malignant glioblastomas grow very rapidly and are generally resistant to either DNA-damaging drugs or gamma-irradiation. If tumor cells could be made more susceptible to cell death with treatments, this would clearly represent a significant improvement in the success of treatment. Recently, telomerase has become a focus of interest among oncologists as a target for treating cancer cells. Telomerase elongates telomeric DNA repeats (TTAGGG)n and is important in protecting and replicating DNA. The vast majority of tumor cells, indeed, express telomerase activity whereas normal somatic cells, except for a few cells, do not. Since telomerase is essential for protecting DNA, we may be able to make tumors more sensitive to treatments with DNA-damaging drugs by inhibiting telomerase activity. In this study, we used cis-diamminedichloroplatinum (cisplatin)-sensitive U87-MG cells and cisplatin-resistant U251-MG of human malignant glioblastoma cell lines. U87-MG cells did not express telomerase activity, whereas telomerase was highly detected in U251-MG cells. Interestingly, inhibition of telomerase with an antisense telomerase expression vector not only decreased telomerase activity but also increased susceptibility to cisplatin-induced apoptotic cell death in U251-MG cells. These findings suggest that treatment with antisense telomerase may represent a new chemosensitisation for tumors resistant to anticancer drugs.
Kondo
Y
Y
Department of Neurosciences, Brain Tumor/Neuro-Oncology Center, The Cleveland Clinic Foundation, Ohio 44195, USA.
Kondo
S
S
Tanaka
Y
Y
Haqqi
T
T
Barna
B P
BP
Cowell
J K
JK
D017209:Apoptosis / Q000187:drug effects*; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005822:Genetic Vectors / Q000138:chemical synthesis; D005909:Glioblastoma / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology*; D006801:Humans; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000235:genetics; D014407:Tumor Cells, Cultured
D016376:Oligonucleotides, Antisense; D019098:Telomerase; D002945:Cisplatin