Inhibition of telomerase activity by a cell-penetrating peptide nucleic acid construct in human melanoma cells.
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.
Villa
R
R
Department of Experimental Oncology, Unit # 10, National Cancer Institute, Via Venezian 1, 20133, Milan, Italy.
Folini
M
M
Lualdi
S
S
Veronese
S
S
Daidone
M G
MG
Zaffaroni
N
N
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
D020135:Peptide Nucleic Acids; D019098:Telomerase