Inhibition of telomerase activity by cisplatin in human testicular cancer cells.
Telomerase, a ribonucleoprotein, elongates and/or maintains telomeres by adding TTAGGG tandem repeat sequences using the RNA component of the enzyme as a template. Enzyme activity appears to be associated with cell immortalisation and malignant progression as telomerase activity has been found in the majority of human tumours, but not in most somatic cells or tissues. Telomerase inhibition has, therefore, been proposed as a novel and potentially selective target for therapeutic intervention. Since telomeric tandem repeats as well as the human telomerase RNA component (hTR) and its gene are guanosine-rich, we examined whether the sequence specific, G-Pt-G, cross-linking agent cisplatin is capable of inhibiting telomerase activity. The TRAP assay was used to measure telomerase activity in cisplatin treated cell extracts and RT-PCR strategies used to examine hTR expression after drug exposure. Cisplatin reduced telomerase activity in a specific and concentration-dependent manner in human testicular tumour cells, whilst doxorubicin, bleomycin, methotrexate, melphalan and transplatin had no effect. It is proposed that telomerase inhibition might be a component of the efficacy of cisplatin in the treatment of testicular cancer.
Burger
A M
AM
Clinical Oncology Unit, University of Bradford, West Yorkshire, U.K.
Double
J A
JA
Newell
D R
DR
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D002945:Cisplatin / Q000494:pharmacology*; D005821:Genetic Techniques; D006801:Humans; D008297:Male; D008558:Melphalan / Q000494:pharmacology; D051379:Mice; D016133:Polymerase Chain Reaction; D013237:Stereoisomerism; D019098:Telomerase / Q000037:antagonists & inhibitors*; D016615:Telomere; D013736:Testicular Neoplasms / Q000201:enzymology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; C034697:transplatin; D019098:Telomerase; D002945:Cisplatin; D008558:Melphalan