INHIBITORY EFFECTS OF TELOMERE-MIMIC PHOSPHOROTHIOATE OLIGONUCLEOTIDES ON VARIOUS HUMAN TUMOR-CELLS IN-VITRO

We tested the cell growth inhibitory effects of telomere-mimic oligome rs, 5'-d(TTAGGG)n-3' where n = 1, 2, 3 or 4 in the following 8 human t umor cell lines: 2780 ovarian carcinoma, HEp-2 squamous cell carcinoma , VAMT-1 mesothelioma. DND-1A melanoma, MOLT-3 ALL, Jurkat lymphoma, D audi Burkitt lymphoma, and JAR choriocarcinoma. As controls, I scrambl ed 6-mer and 2 scrambled 24-mers were tested. Among the compounds rest ed, the 6-mer and 22-mer were not active in any of the cell lines stud ied. Increases in the length of oligonucleotides from 18- to 24-mer re sulted in increased cell growth inhibitory activity in sensitive cell suspension cultures, MOLT-S ALL and lymphoma were generally more sensi tive than the monolayers (24-mer ID90 = similar to 3 mu M). While the inhibitory effects of authentic 24-mer oligomer were more pronounced t han 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-LA 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 a candidate compound for the treatment of leukemia/lymphoma.