|
|
 Previous Article | Table of Contents | Next Article 
Blood, 15 November 2000, Vol. 96, No. 10, pp. 3537-3543
NEOPLASIA
Deoxyadenosine analogs induce programmed cell death in chronic
lymphocytic leukemia cells by damaging the DNA and by directly
affecting the mitochondria
Davide Genini,
Souichi Adachi,
Qi Chao,
David W. Rose,
Carlos J. Carrera,
Howard B. Cottam,
Dennis A. Carson, and
Lorenzo M. Leoni
From the Department of Medicine and The Sam and Rose
Stein Institute for Research on Aging and the Department of
Medicine/Division of Endocrinology and Metabolism, Whittier Diabetes
Program, University of California, San Diego, La Jolla, CA.
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 mitochondria, that
2-chloro-2'-deoxyadenosine (2CdA) and
2-choloro-2'-ara-fluorodeoxyadenosine (CaFdA) disrupt the integrity of
mitochondria from primary chronic lymphocytic leukemia (B-CLL) cells.
The nucleoside-induced damage leads to the release of the pro-apoptotic
mitochondrial proteins cytochrome c and apoptosis-inducing factor. The
other adenine deoxynucleosides tested displayed comparable DNA-damaging
potency but did not affect mitochondrial function. Interference with
mitochondrial integrity, thus, may be a factor in the potent cytotoxic
effects of 2CdA and CaFdA toward nondividing lymphocytes.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
A. M. McElligott, E. N. Maginn, L. M. Greene, S. McGuckin, A. Hayat, P. V. Browne, S. Butini, G. Campiani, M. A. Catherwood, E. Vandenberghe, et al.
The Novel Tubulin-Targeting Agent Pyrrolo-1,5-Benzoxazepine-15 Induces Apoptosis in Poor Prognostic Subgroups of Chronic Lymphocytic Leukemia
Cancer Res.,
November 1, 2009;
69(21):
8366 - 8375.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Gine, M. Crespo, A. Muntanola, E. Calpe, M. J. Baptista, N. Villamor, E. Montserrat, and F. Bosch
Induction of histone H1.2 cytosolic release in chronic lymphocytic leukemia cells after genotoxic and non-genotoxic treatment
Haematologica,
January 1, 2008;
93(1):
75 - 82.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. E. Karp, R. M. Ricklis, K. Balakrishnan, J. Briel, J. Greer, S. D. Gore, B. D. Smith, M. A. McDevitt, H. Carraway, M. J. Levis, et al.
A phase 1 clinical-laboratory study of clofarabine followed by cyclophosphamide for adults with refractory acute leukemias
Blood,
September 15, 2007;
110(6):
1762 - 1769.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Kroemer, L. Galluzzi, and C. Brenner
Mitochondrial Membrane Permeabilization in Cell Death
Physiol Rev,
January 1, 2007;
87(1):
99 - 163.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Balakrishnan, R. Nimmanapalli, F. Ravandi, M. J. Keating, and V. Gandhi
Forodesine, an inhibitor of purine nucleoside phosphorylase, induces apoptosis in chronic lymphocytic leukemia cells
Blood,
October 1, 2006;
108(7):
2392 - 2398.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Kojima, M. Konopleva, T. McQueen, S. O'Brien, W. Plunkett, and M. Andreeff
Mdm2 inhibitor Nutlin-3a induces p53-mediated apoptosis by transcription-dependent and transcription-independent mechanisms and may overcome Atm-mediated resistance to fludarabine in chronic lymphocytic leukemia
Blood,
August 1, 2006;
108(3):
993 - 1000.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Gandhi, W. Plunkett, P. L. Bonate, M. Du, B. Nowak, S. Lerner, and M. J. Keating
Clinical and Pharmacokinetic Study of Clofarabine in Chronic Lymphocytic Leukemia: Strategy for Treatment.
Clin. Cancer Res.,
July 1, 2006;
12(13):
4011 - 4017.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
U. Fischer and K. Schulze-Osthoff
New Approaches and Therapeutics Targeting Apoptosis in Disease
Pharmacol. Rev.,
June 1, 2005;
57(2):
187 - 215.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Balakrishnan, C. M. Stellrecht, D. Genini, M. Ayres, W. G. Wierda, M. J. Keating, L. M. Leoni, and V. Gandhi
Cell death of bioenergetically compromised and transcriptionally challenged CLL lymphocytes by chlorinated ATP
Blood,
June 1, 2005;
105(11):
4455 - 4462.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Rotem, A. Heyfets, O. Fingrut, D. Blickstein, M. Shaklai, and E. Flescher
Jasmonates: Novel Anticancer Agents Acting Directly and Selectively on Human Cancer Cell Mitochondria
Cancer Res.,
March 1, 2005;
65(5):
1984 - 1993.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Rosenwald, E. Y. Chuang, R. E. Davis, A. Wiestner, A. A. Alizadeh, D. C. Arthur, J. B. Mitchell, G. E. Marti, D. H. Fowler, W. H. Wilson, et al.
Fludarabine treatment of patients with chronic lymphocytic leukemia induces a p53-dependent gene expression response
Blood,
September 1, 2004;
104(5):
1428 - 1434.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. P. Mone, P. Huang, H. Pelicano, C. M. Cheney, J. M. Green, J. Y. Tso, A. J. Johnson, S. Jefferson, T. S. Lin, and J. C. Byrd
Hu1D10 induces apoptosis concurrent with activation of the AKT survival pathway in human chronic lymphocytic leukemia cells
Blood,
March 1, 2004;
103(5):
1846 - 1854.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Lai, C.-M. Tse, and J. D. Unadkat
Mitochondrial Expression of the Human Equilibrative Nucleoside Transporter 1 (hENT1) Results in Enhanced Mitochondrial Toxicity of Antiviral Drugs
J. Biol. Chem.,
February 6, 2004;
279(6):
4490 - 4497.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. L. Aron, M. R. Parthun, G. Marcucci, S. Kitada, A. P. Mone, M. E. Davis, T. Shen, T. Murphy, J. Wickham, C. Kanakry, et al.
Depsipeptide (FR901228) induces histone acetylation and inhibition of histone deacetylase in chronic lymphocytic leukemia cells concurrent with activation of caspase 8-mediated apoptosis and down-regulation of c-FLIP protein
Blood,
July 15, 2003;
102(2):
652 - 658.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Ceruti, E. Beltrami, P. Matarrese, A. Mazzola, F. Cattabeni, W. Malorni, and M. P. Abbracchio
A Key Role for Caspase-2 and Caspase-3 in the Apoptosis Induced by 2-Chloro-2'-deoxy-adenosine (Cladribine) and 2-Chloro-adenosine in Human Astrocytoma Cells
Mol. Pharmacol.,
June 1, 2003;
63(6):
1437 - 1447.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. T. Jones, K. Ganeshaguru, R. J. Anderson, T. R. Jackson, K. R. Bruckdorfer, S. Y. Low, L. Palmqvist, H. G. Prentice, A. V. Hoffbrand, A. B. Mehta, et al.
Albumin activates the AKT signaling pathway and protects B-chronic lymphocytic leukemia cells from chlorambucil- and radiation-induced apoptosis
Blood,
April 15, 2003;
101(8):
3174 - 3180.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. M. Pedersen, S. Kitada, A. Schimmer, Y. Kim, J. M. Zapata, L. Charboneau, L. Rassenti, M. Andreeff, F. Bennett, M. B. Sporn, et al.
The triterpenoid CDDO induces apoptosis in refractory CLL B cells
Blood,
September 26, 2002;
100(8):
2965 - 2972.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Chandra, E. Mansson, V. Gogvadze, S. H. Kaufmann, F. Albertioni, and S. Orrenius
Resistance of leukemic cells to 2-chlorodeoxyadenosine is due to a lack of calcium-dependent cytochrome c release
Blood,
January 15, 2002;
99(2):
655 - 663.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. D. Batiuk, C. Schnizlein-Bick, Z. Plotkin, and P. C. Dagher
Guanine nucleosides and Jurkat cell death: roles of ATP depletion and accumulation of deoxyribonucleotides
Am J Physiol Cell Physiol,
December 1, 2001;
281(6):
C1776 - C1784.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. T. Lang, M. Selner, J. D. Young, and C. E. Cass
Acquisition of Human Concentrative Nucleoside Transporter 2 (hCNT2) Activity by Gene Transfer Confers Sensitivity to Fluoropyrimidine Nucleosides in Drug-Resistant Leukemia Cells
Mol. Pharmacol.,
November 1, 2001;
60(5):
1143 - 1152.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
