Inhibitory effects of telomere-mimic phosphorothioate oligonucleotides on various human tumor cells in vitro.
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.
Ohnuma
T
T
Department of Medicine, Mount Sinai Medical Center, New York, NY 10029, USA.
Li
F L
FL
Holland
J F
JF
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*
D006131:Growth Inhibitors; D009841:Oligonucleotides; D013873:Thionucleotides