Inhibitory effect of telomere-mimic phosphorothioate oligodeoxy nucleotides (S-ODNS) on human tumor cell lines

To clarify the inhibitory effect of telomere-mimic oligonucleotides on huma n cancer cell lines, we synthesized 18-mers (18T; n = 3), 24-mers (24T; n = 4) and 30-mers (30T; n = 5) of telomere-mimic phosphorothioate oligodeoxy nucleotides [5'-d(TTA GGG)n-3'] and examined their effects on the prolifera tion of human tumor cells by XTT assay. After 7 days of continuous exposure to 24T and 30T at concentrations ranging from 0.1 to 10 mu M, concentratio n-dependent cell growth inhibition was observed in MCF-7 clone E3, ZR-75-1, MDA-MB 231, Cole 201 and WiDr. All of these cell lines highly expressed te lomerase using the telomeric repeat amplification protocol. None of these t umor cell lines were affected by 18T. In MCF-7, ZR-75-1 and Cole 201 cell l ines, a more than 50 % growth inhibition was obtained by 3 mu M of 24T and 30T whereas, in MDA-MB 231 and WiDr cell lines, cell growth inhibition was less than 50%. 30T was more effective than 24T. Estrogen-dependent growth o f both MCF-7 and ZR-75-1 was inhibited by 3 mu M of 24T and 30T, however, i n the absence of estrogen, no growth inhibition was seen. The MCF-10A cell line, which was developed from normal human breast tissue and expressed tel omerase only weakly, was inhibited by 10 mu M of 18T. In conclusion, these observations indicate that S-ODNs inhibit tumor growth in cell lines expres sing telomerase in a concentration-dependent manner and that cell growth in hibition is dependent on the length of S-ODNs. In addition, the short-lengt h S-ODNs may inhibit growth of cells weakly expressing telomerase, but not of cells with high telomerase expression.