Počet záznamů: 1

Distinct modulation of telomere length in two T-lymphoblastic leukemia cell lines by cytotoxic nucleoside phosphonates PMEG and PMEDAP

  1. 1.
    0346304 - UOCHB-X 2011 RIV NL eng J - Článek v odborném periodiku
    Hájek, Miroslav - Cvilink, Viktor - Votruba, Ivan - Holý, Antonín - Mertlíková-Kaiserová, Helena
    Distinct modulation of telomere length in two T-lymphoblastic leukemia cell lines by cytotoxic nucleoside phosphonates PMEG and PMEDAP.
    European Journal of Pharmacology. Roč. 643, č. 1 (2010), s. 6-12 ISSN 0014-2999
    Grant CEP: GA MŠk 1M0508; GA AV ČR 1QS400550501
    Výzkumný záměr: CEZ:AV0Z40550506
    Klíčová slova: acyclic nucleoside phosphonates * PMEG * PMEDAP * telomere length * telomerase inhibition
    Kód oboru RIV: CC - Organická chemie
    Impakt faktor: 2.737, rok: 2010

    We have previously shown that PMEG diphosphate and PMEDAP diphosphate inhibit the enzymatic activity of human telomerase in a cell-free assay. Here, we investigated the ability of PMEG and PMEDAP to induce telomere shortening and telomerase inhibition in two T-cell leukemia cell lines. Both PMEDAP and PMEG induced telomere shortening in CCRF-CEM cells after 9 weeks of exposure while the effect of the compounds on telomere length in MOLT-4 cells was the opposite. No correlation between telomerase activity and telomere length was found. Both compounds also down-regulated the expression of hTERT and c-myc mRNA in both cell lines. In conclusion, PMEDAP and PMEG are able to modulate telomere length in leukemic cells and this effect is cell-type specific. It is neither due to telomerase inhibition nor impairment of hTERT expression and it is likely to be telomerase-independent.
    Trvalý link: http://hdl.handle.net/11104/0187372