title: Attenuation of telomerase activity does not increase sensitivity of human melanoma cells to anticancer agents.
abstract: In tumour cells, replicative immortality is attained through stabilisation of telomeres by telomerase. Recent evidence suggests that telomerase plays an anti-apoptotic role. Since apoptosis is the primary mode of cell death induced by several drugs, telomerase could be involved in determining the chemosensitivity profile of tumour cells. We investigated whether inhibition of telomerase activity through a hammerhead ribozyme targeting the RNA template of telomerase influences the susceptibility of human melanoma cells to a variety of anticancer agents (platinum compounds, taxanes, topoisomerase I inhibitors). The ribozyme sequence was inserted into an expression vector and the JR8 human melanoma cell line was transfected with it. The cell clones obtained showed a reduced telomerase activity. Growth inhibition curves generated after exposure of ribozyme-transfectant clones to individual drugs were superimposable to those obtained from parental cells. Moreover, telomerase inhibition did not promote apoptosis as a cellular response to drug treatment. Overall, our results indicate that downregulation of telomerase activity does not increase the sensitivity of melanoma cells to anticancer drugs.
authors.affiliation: Dipartimento di Oncologia Sperimentale, Istituto Nazionale per lo Studio e la Cura dei Tumori, Via Venezian 1, I-20133, Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Folini
authors.forename: C
authors.initials: C
authors.lastname: De Marco
authors.forename: L
authors.initials: L
authors.lastname: Orlandi
authors.forename: M G
authors.initials: MG
authors.lastname: Daidone
authors.forename: N
authors.initials: N
authors.lastname: Zaffaroni
mesh_terms: D000970:Antineoplastic Agents / Q000378:metabolism / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000037:antagonists & inhibitors*; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D019098:Telomerase