title: Inhibitory effects of telomere-mimic phosphorothioate oligonucleotides on various human tumor cells in vitro.
abstract: We tested the cell growth inhibitory effects of telomere-mimic oligomers, 5'-d(TTAGGG)n-3' where n = 1, 2, 3 or 4 in the following 8 human tumor cell lines: 2780 ovarian carcinoma, HEp-2 squamous cell carcinoma, VAMT-1 mesothelioma, DND-1A melanoma, MOLT-3 ALL, Jurkat lymphoma, Daudi Burkitt lymphoma, and JAR choriocarcinoma. As controls, 1 scrambled 6-mer and 2 scrambled 24-mers were tested. Among the compounds tested, the 6-mer and 12-mer were not active in any of the cell lines studied. Increases in the length of oligonucleotides from 18- to 24-mer resulted in increased cell growth inhibitory activity in sensitive cell lines. Cells in suspension cultures, MOLT-3 ALL and Daudi Burkitt lymphoma were generally more sensitive than the monolayers (24-mer ID90 = -3 microM). While the inhibitory effects of authentic 24-mer oligomer were more pronounced than the scrambled oligomers, both of the scrambled 24-mers also showed some degree of inhibitory activity. Except for modest activity of the 24-mer in 2 cell lines, DND-1A and 2780, none of the compounds tested were active against solid tumor cell lines. These data indicate that further study of the telomere-mimic 24-mer is warranted as candidate compound for the treatment of leukemia/lymphoma.
authors.affiliation: Department of Medicine, Mount Sinai Medical Center, New York, NY 10029, USA.
authors.forename: T
authors.initials: T
authors.lastname: Ohnuma
authors.forename: F L
authors.initials: FL
authors.lastname: Li
authors.forename: J F
authors.initials: JF
authors.lastname: Holland
mesh_terms: D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D009841:Oligonucleotides / Q000008:administration & dosage* / Q000737:chemistry; D016615:Telomere; D013873:Thionucleotides / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects*
chemical_list: D006131:Growth Inhibitors; D009841:Oligonucleotides; D013873:Thionucleotides