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

SYSNO ASEP	0346304
Document Type	J - Journal Article
R&D Document Type	Journal Article
Subsidiary J	Článek ve WOS
Title	Distinct modulation of telomere length in two T-lymphoblastic leukemia cell lines by cytotoxic nucleoside phosphonates PMEG and PMEDAP
Author(s)	Hájek, Miroslav (UOCHB-X)_{RID, ORCID} Cvilink, Viktor (UOCHB-X) Votruba, Ivan (UOCHB-X)_RID Holý, Antonín (UOCHB-X) Mertlíková-Kaiserová, Helena (UOCHB-X)_{RID, ORCID}
Number of authors	5
Source Title	European Journal of Pharmacology. - : Elsevier - ISSN 0014-2999 Roč. 643, č. 1 (2010), s. 6-12
Number of pages	7 s.
Language	eng - English
Country	NL - Netherlands
Keywords	acyclic nucleoside phosphonates ; PMEG ; PMEDAP ; telomere length ; telomerase inhibition
Subject RIV	CC - Organic Chemistry
R&D Projects	1M0508 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
	1QS400550501 GA AV ČR - Academy of Sciences of the Czech Republic (AV ČR)
CEZ	AV0Z40550506 - UOCHB-X (2005-2011)
UT WOS	000280627700002
DOI	10.1016/j.ejphar.2010.06.006
Annotation	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.
Workplace	Institute of Organic Chemistry and Biochemistry
Contact	asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Viktorie Chládková, Tel.: 232 002 434
Year of Publishing	2011

Number of the records: 1