DOI: 10.1073/pnas.95.16.9567. Induction of an apoptotic program in cell-free extracts by 2-chloro-2′-deoxyadenosine 5′-triphosphate and cytochrome c

Induction of an apoptotic program in cell-free extracts by 2-chloro-2′-deoxyadenosine 5′-triphosphate and cytochrome c

10.1073/pnas.95.16.9567

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Adenine deoxynucleosides, such as 2-chloro-2′-deoxyadenosine (2CdA) induce apoptosis in quiescent lymphocytes, and are thus useful drugs for the treatment of indolent lymphoproliferative diseases. However, it has remained puzzling why deoxyadenosine and its analogs are toxic to a cell that is not undergoing replicative DNA synthesis. The present experiments demonstrate that the 5′-triphosphate metabolite of 2CdA (2CdA-5′-triphosphate), similar to dATP, can cooperate with cytochromecand Apaf-1 to activate caspase-3 in a cell free system. Chronic lymphocytic leukemia cells and normal peripheral blood lymphocytes expressed both caspase-3 and apoptotic protease activating factor 1. Incubation of the lymphocytes with 2CdA induced caspase-3 activation prior to DNA degradation and cell death. Stimulation of the caspase proteolytic cascade by 2CdA-5′-triphosphate, in the context of DNA strand break formation, may provide an explanation for the potent cytotoxic effects of 2CdA toward nondividing lymphocytes.

Bibliography

Leoni, L. M., Chao, Q., Cottam, H. B., Genini, D., Rosenbach, M., Carrera, C. J., Budihardjo, I., Wang, X., & Carson, D. A. (1998). Induction of an apoptotic program in cell-free extracts by 2-chloro-2â²-deoxyadenosine 5â²-triphosphate and cytochrome c. Proceedings of the National Academy of Sciences, 95(16), 9567â9571.

Authors 9

Lorenzo M. Leoni (first)
Qi Chao (additional)
Howard B. Cottam (additional)
Davide Genini (additional)
Michael Rosenbach (additional)
Carlos J. Carrera (additional)
Imawati Budihardjo (additional)
Xiaodong Wang (additional)
Dennis A. Carson (additional)

References 35 Referenced 100

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M Castedo, T Hirsch, S A Susin, N Zamzami, P Marchetti, A Macho, G Kroemer J Immunol 157, 512–521 (1996). (10.4049/jimmunol.157.2.512) / J Immunol by Castedo M (1996)
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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:40 a.m.)
Deposited	2 years, 4 months ago (April 22, 2023, 8:24 a.m.)
Indexed	1 year, 9 months ago (Nov. 21, 2023, 1:22 a.m.)
Issued	27 years ago (Aug. 4, 1998)
Published	27 years ago (Aug. 4, 1998)
Published Online	27 years ago (Aug. 4, 1998)
Published Print	27 years ago (Aug. 4, 1998)

Funders 0

None

BibTeX

@article{Leoni_1998, title={Induction of an apoptotic program in cell-free extracts by 2-chloro-2′-deoxyadenosine 5′-triphosphate and cytochrome c}, volume={95}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.95.16.9567}, DOI={10.1073/pnas.95.16.9567}, number={16}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Leoni, Lorenzo M. and Chao, Qi and Cottam, Howard B. and Genini, Davide and Rosenbach, Michael and Carrera, Carlos J. and Budihardjo, Imawati and Wang, Xiaodong and Carson, Dennis A.}, year={1998}, month=aug, pages={9567–9571} }

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