Inhibitory effect of telomere-mimic phosphorothioate oligodeoxy nucleotides (S-ODNS) on human tumor cell lines.
Identifieur interne : 002615 ( PubMed/Curation ); précédent : 002614; suivant : 002616Inhibitory 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. OhnumaSource :
- Oncology [ 0030-2414 ] ; 1999.
Descripteurs français
- KwdFr :
- Cellules cancéreuses en culture, Humains, Oligodésoxyribonucléotides antisens, Oligonucléotides, Telomerase (génétique), Telomerase (métabolisme), Thionucléotides, Tumeurs du côlon (enzymologie), Tumeurs du côlon (génétique), Tumeurs du côlon (métabolisme), Tumeurs du sein (enzymologie), Tumeurs du sein (génétique), Tumeurs du sein (métabolisme), Télomère.
- MESH :
- enzymologie : Tumeurs du côlon, Tumeurs du sein.
- génétique : Telomerase, Tumeurs du côlon, Tumeurs du sein.
- métabolisme : Telomerase, Tumeurs du côlon, Tumeurs du sein.
- Cellules cancéreuses en culture, Humains, Oligodésoxyribonucléotides antisens, Oligonucléotides, Thionucléotides, Télomère.
English descriptors
- KwdEn :
- Breast Neoplasms (enzymology), Breast Neoplasms (genetics), Breast Neoplasms (metabolism), Colonic Neoplasms (enzymology), Colonic Neoplasms (genetics), Colonic Neoplasms (metabolism), Humans, Oligodeoxyribonucleotides, Antisense, Oligonucleotides, Telomerase (genetics), Telomerase (metabolism), Telomere, Thionucleotides, Tumor Cells, Cultured.
- MESH :
- chemical , genetics : Telomerase.
- chemical , metabolism : Telomerase.
- chemical : Oligodeoxyribonucleotides, Antisense, Oligonucleotides, Thionucleotides.
- enzymology : Breast Neoplasms, Colonic Neoplasms.
- genetics : Breast Neoplasms, Colonic Neoplasms.
- metabolism : Breast Neoplasms, Colonic Neoplasms.
- Humans, Telomere, Tumor Cells, Cultured.
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
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pubmed:10545800Le document en format XML
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<term>Colonic Neoplasms (enzymology)</term>
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<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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<keywords scheme="KwdFr" xml:lang="fr"><term>Cellules cancéreuses en culture</term>
<term>Humains</term>
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<term>Telomerase (génétique)</term>
<term>Telomerase (métabolisme)</term>
<term>Thionucléotides</term>
<term>Tumeurs du côlon (enzymologie)</term>
<term>Tumeurs du côlon (génétique)</term>
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<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>Colonic Neoplasms</term>
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<term>Oligodésoxyribonucléotides antisens</term>
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<front><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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<Abstract><AbstractText>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.</AbstractText>
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