title: Inhibition of telomerase activity by a cell-penetrating peptide nucleic acid construct in human melanoma cells.
abstract: We investigated the effect of two peptide nucleic acids (PNAs), which are complementary to the RNA component of human telomerase, on the catalytic activity of the enzyme. PNAs induced a dose-dependent reduction of telomerase activity in cell extracts from human melanoma cell lines and surgical specimens. To down-regulate telomerase in intact cells, we generated a chimeric molecule synthesized by coupling the 13-mer PNA to the Antennapedia peptide. The PNA construct induced a dose- and time-dependent inhibition of telomerase activity. However, a 20-day exposure to the PNA construct only caused a slight increase in melanoma cell doubling time and failed to induce any telomere shortening.
authors.affiliation: Department of Experimental Oncology, Unit # 10, National Cancer Institute, Via Venezian 1, 20133, Milan, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Villa
authors.forename: M
authors.initials: M
authors.lastname: Folini
authors.forename: S
authors.initials: S
authors.lastname: Lualdi
authors.forename: S
authors.initials: S
authors.lastname: Veronese
authors.forename: M G
authors.initials: MG
authors.lastname: Daidone
authors.forename: N
authors.initials: N
authors.lastname: Zaffaroni
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D019921:Biotinylation; D002455:Cell Division / Q000187:drug effects; D002463:Cell Membrane Permeability; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008545:Melanoma / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D008856:Microscopy, Fluorescence; D020135:Peptide Nucleic Acids / Q000138:chemical synthesis / Q000494:pharmacology*; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016615:Telomere / Q000187:drug effects; D014407:Tumor Cells, Cultured
chemical_list: D020135:Peptide Nucleic Acids; D019098:Telomerase