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

Identifieur interne : 003804 ( Main/Exploration ); précédent : 003803; suivant : 003805

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

Auteurs : T. Saeki [Japon] ; S. Takashima ; M. Tachibana ; M. Koga ; E. Hiyama ; D S Salomon ; J F Holland ; T. Ohnuma

Source :

RBID : pubmed:10545800

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English descriptors

Abstract

To clarify the inhibitory effect of telomere-mimic oligonucleotides on human 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 proliferation 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 microM, concentration-dependent cell growth inhibition was observed in MCF-7 clone E3, ZR-75-1, MDA-MB 231, Colo 201 and WiDr. All of these cell lines highly expressed telomerase using the telomeric repeat amplification protocol. None of these tumor cell lines were affected by 18T. In MCF-7, ZR-75-1 and Colo 201 cell lines, a more than 50% growth inhibition was obtained by 3 microM 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 of both MCF-7 and ZR-75-1 was inhibited by 3 microM of 24T and 30T, however, in the absence of estrogen, no growth inhibition was seen. The MCF-10A cell line, which was developed from normal human breast tissue and expressed telomerase only weakly, was inhibited by 10 microM of 18T. In conclusion, these observations indicate that S-ODNs inhibit tumor growth in cell lines expressing telomerase in a concentration-dependent manner and that cell growth inhibition is dependent on the length of S-ODNs. In addition, the short-length S-ODNs may inhibit growth of cells weakly expressing telomerase, but not of cells with high telomerase expression.

DOI: 10.1159/000055272
PubMed: 10545800


Affiliations:


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Le document en format XML

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<term>Breast Neoplasms (enzymology)</term>
<term>Breast Neoplasms (genetics)</term>
<term>Breast Neoplasms (metabolism)</term>
<term>Colonic Neoplasms (enzymology)</term>
<term>Colonic Neoplasms (genetics)</term>
<term>Colonic Neoplasms (metabolism)</term>
<term>Humans</term>
<term>Oligodeoxyribonucleotides, Antisense</term>
<term>Oligonucleotides</term>
<term>Telomerase (genetics)</term>
<term>Telomerase (metabolism)</term>
<term>Telomere</term>
<term>Thionucleotides</term>
<term>Tumor Cells, Cultured</term>
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<term>Cellules cancéreuses en culture</term>
<term>Humains</term>
<term>Oligodésoxyribonucléotides antisens</term>
<term>Oligonucléotides</term>
<term>Telomerase (génétique)</term>
<term>Telomerase (métabolisme)</term>
<term>Thionucléotides</term>
<term>Tumeurs du côlon (enzymologie)</term>
<term>Tumeurs du côlon (génétique)</term>
<term>Tumeurs du côlon (métabolisme)</term>
<term>Tumeurs du sein (enzymologie)</term>
<term>Tumeurs du sein (génétique)</term>
<term>Tumeurs du sein (métabolisme)</term>
<term>Télomère</term>
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<term>Telomerase</term>
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<term>Telomerase</term>
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<term>Oligodeoxyribonucleotides, Antisense</term>
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<term>Tumeurs du côlon</term>
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<div type="abstract" xml:lang="en">To clarify the inhibitory effect of telomere-mimic oligonucleotides on human 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 proliferation 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 microM, concentration-dependent cell growth inhibition was observed in MCF-7 clone E3, ZR-75-1, MDA-MB 231, Colo 201 and WiDr. All of these cell lines highly expressed telomerase using the telomeric repeat amplification protocol. None of these tumor cell lines were affected by 18T. In MCF-7, ZR-75-1 and Colo 201 cell lines, a more than 50% growth inhibition was obtained by 3 microM 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 of both MCF-7 and ZR-75-1 was inhibited by 3 microM of 24T and 30T, however, in the absence of estrogen, no growth inhibition was seen. The MCF-10A cell line, which was developed from normal human breast tissue and expressed telomerase only weakly, was inhibited by 10 microM of 18T. In conclusion, these observations indicate that S-ODNs inhibit tumor growth in cell lines expressing telomerase in a concentration-dependent manner and that cell growth inhibition is dependent on the length of S-ODNs. In addition, the short-length S-ODNs may inhibit growth of cells weakly expressing telomerase, but not of cells with high telomerase expression.</div>
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