2000
DOI: 10.1182/blood.v96.10.3537.h8003537_3537_3543
|View full text |Cite
|
Sign up to set email alerts
|

Deoxyadenosine analogs induce programmed cell death in chronic lymphocytic leukemia cells by damaging the DNA and by directly affecting the mitochondria

Abstract: Adenine deoxynucleosides induce apoptosis in quiescent lymphocytes and are thus useful drugs for the treatment of indolent lymphoproliferative diseases. To explain why deoxyadenosine and its analogs are toxic to a cell that is not undergoing replicative DNA synthesis, several mechanisms have been proposed, including the direct binding of dATP to the pro-apoptotic factor Apaf-1 and the activation of the caspase-9 and -3 pathways. In this study it is shown, by means of several assays on whole cells and isolated … Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
2
1

Citation Types

3
83
0
7

Year Published

2003
2003
2021
2021

Publication Types

Select...
8

Relationship

0
8

Authors

Journals

citations
Cited by 105 publications
(93 citation statements)
references
References 33 publications
3
83
0
7
Order By: Relevance
“…Other polyhydroxy-substituted benzohydroxamic acid derivatives, amidox and didox, which also inhibit ribonucleotide reductase in leukaemia cells (Tihan et al 1991), induce apoptosis via the activation of caspases (Grusch et al 2001). Chlorodeoxyadenosin, an ribonucleotide reductase inhibitor, was also found to induce DNA damage, mitochondrial dysfunction, release of cytochrome c into the cytosol, and activation of the caspase pathway (Genini et al 2000). These findings were supported by our experiment results.…”
Section: Discussionsupporting
confidence: 83%
“…Other polyhydroxy-substituted benzohydroxamic acid derivatives, amidox and didox, which also inhibit ribonucleotide reductase in leukaemia cells (Tihan et al 1991), induce apoptosis via the activation of caspases (Grusch et al 2001). Chlorodeoxyadenosin, an ribonucleotide reductase inhibitor, was also found to induce DNA damage, mitochondrial dysfunction, release of cytochrome c into the cytosol, and activation of the caspase pathway (Genini et al 2000). These findings were supported by our experiment results.…”
Section: Discussionsupporting
confidence: 83%
“…Incorporation of F-AraA-TP or CdA-TP into DNA by the repair mechanisms leads to the progressive accumulation of DNA single-strand breaks eventually responsible for apoptosis by both p53-dependent and p53-independent pathways (Sandoval et al, 1996). Another consequence of these treatments is the direct activation of the caspase-9 and caspase-3 pathways by F-AraA-TP and CdA-TP, which are nucleotide activators of Apaf-1 (Genini et al, 2000). Moreover, F-AraA and CdA also alter gene transcription, resulting in depletion of proteins required for cell survival.…”
Section: Deoxyribonucleoside Analoguesmentioning
confidence: 99%
“…In these respects, and in contrast to previous studies, the present study investigated the mechanism of CAFdA resistance intensively and extensively. (10)(11)(12)(13)(14) The resistant variants developed here exhibited cross-resistance against similar nucleoside analogs ( Table 1). Because the activation pathway is basically the same, (30) such crossresistance may be caused by the decrease in transport capacity and the reduced dCK.…”
Section: Discussionmentioning
confidence: 89%
“…CAFdATP is incorporated into DNA, thereby terminating DNA elongation and eventually inducing apoptosis. (12)(13)(14)(15)(16)(17) CAFdA also induces apoptosis via direct mitochondrial damage. (13) Pharmacological understanding of action of CAFdA is crucial to its optimal administration.…”
mentioning
confidence: 99%
See 1 more Smart Citation