Role of the phosphorolysis of deoxyadenosine in the cytotoxic effect of the combination of deoxyadenosine and deoxycoformycin on a human colon carcinoma cell line (LoVo)

Giorgelli, Francesco; Giannecchini, Michela; Bemi, Valentina; Turchi, G.; Sgarrella, Francesco; Tozzi, Maria Grazia; Camici, Marcella

doi:10.1002/1097-4644(20010201)80:2<241::aid-jcb130>3.0.co;2-q

Cited by 7 publications

(2 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Linearity with time and protein concentration was observed for all enzyme assays. Extracts for the determination of ATP: adenosine 5′‐phosphotransferase (EC 2.7.1.20) (adenosine kinase, AdoK), ADA and purine‐nucleoside: orthophosphate ribosyltransferase (EC 2.4.2.1) (purine nucleoside phosphorylase, PNP) activities were prepared from SH‐SY5Y cells essentially according to Giorgelli et al []. A radioenzymatic assay was applied for the determination of AdoK [Camici et al, ].…”

Section: Methodsmentioning

confidence: 99%

Mitochondrial Damage and Apoptosis Induced by Adenosine Deaminase Inhibition and Deoxyadenosine in Human Neuroblastoma Cell Lines

Garcia‐Gil

Tozzi²,

Balestri³

et al. 2015

J of Cellular Biochemistry

Self Cite

View full text Add to dashboard Cite

The treatment with deoxycoformycin, a strong adenosine deaminase inhibitor, in combination with deoxyadenosine, causes apoptotic cell death of two human neuroblastoma cell lines, SH-SY5Y and LAN5. Herein we demonstrate that, in SH-SY5Y cells, this combination rapidly decreases mitochondrial reactive oxygen species and, in parallel, increases mitochondrial mass, while, later, induces nuclear fragmentation, and activation of caspase-8, -9, and -3. In previous papers we have shown that a human astrocytoma cell line, subjected to the same treatment, undergoes apoptotic death as well. Therefore, both astrocytoma and neuroblastoma cell lines undergo apoptotic death following the combined treatment with deoxycoformycin and deoxyadenosine, but several differences have been found in the mode of action, possibly reflecting a different functional and metabolic profile of the two cell lines. Overall this work indicates that the neuroblastoma cell lines, like the line of astrocytic origin, are very sensitive to purine metabolism perturbation thus suggesting new therapeutic approaches to nervous system tumors. J. Cell. Biochem. 117: 1671-1679, 2016. © 2015 Wiley Periodicals, Inc.

show abstract

Section: Methodsmentioning

confidence: 99%

Mitochondrial Damage and Apoptosis Induced by Adenosine Deaminase Inhibition and Deoxyadenosine in Human Neuroblastoma Cell Lines

Garcia‐Gil

Tozzi²,

Balestri³

et al. 2015

J of Cellular Biochemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…3,7 The combination of dAdo and deoxycoformycin has been found to affect the growth of a human colon carcinoma cell line. 8,9 It has also been reported that high concentration of dAdo inhibits DNA synthesis and cell division in animals and also contributes to the dialysis-induced immune deciency. 10 dAdo has been used as a useful precursor in the synthesis of a wide variety of antiviral, antitumor and antileukemic drugs and has also exhibited a cardio protective action.…”

Section: Introductionmentioning

confidence: 99%

A carbon ion beam irradiated MWCNT/AuNPs composite sensor for a sensitive assay of purine-nucleosides of DNA

2015

View full text Add to dashboard Cite

show abstract

2′‐Deoxyadenosine causes apoptotic cell death in a human colon carcinoma cell line

Giannecchini

D'Innocenzo

Pesi

et al. 2003

J Biochem & Molecular Tox

Self Cite

View full text Add to dashboard Cite

The combination of 2'-deoxyadenosine and 2'-deoxycoformycin is toxic for the human colon carcinoma cell line LoVo. In this study we investigated the mode of action of the two compounds and have found that they promote apoptosis. The examination by fluorescence microscopy of the cells treated with the combination revealed the characteristic morphology associated with apoptosis, such as chromatin condensation and nuclear fragmentation. The occurrence of apoptosis was also confirmed by the release of cytochrome c and the proteolytic processing of procaspase-3 in cells subjected to the treatment. To exert its triggering action on the apoptotic process, 2'-deoxyadenosine enters the cells through an equilibrative nitrobenzyl-thioinosine-insensitive carrier, and must be phosphorylated by intracellular kinases. Indeed, in the present work we demonstrate by analysis of the intracellular metabolic derivatives of 2'-deoxyadenosine that, as suggested by our previous findings, in the incubation performed with 2'-deoxyadenosine and 2'-deoxycoformycin, an appreciable amount of dATP was formed. Conversely, when also an inhibitor of adenosine kinase was added to the incubation mixture, dATP was not formed, and the toxic and apoptotic effect of the combination was completely reverted.

show abstract

Role of the phosphorolysis of deoxyadenosine in the cytotoxic effect of the combination of deoxyadenosine and deoxycoformycin on a human colon carcinoma cell line (LoVo)

Cited by 7 publications

References 14 publications

Mitochondrial Damage and Apoptosis Induced by Adenosine Deaminase Inhibition and Deoxyadenosine in Human Neuroblastoma Cell Lines

Mitochondrial Damage and Apoptosis Induced by Adenosine Deaminase Inhibition and Deoxyadenosine in Human Neuroblastoma Cell Lines

A carbon ion beam irradiated MWCNT/AuNPs composite sensor for a sensitive assay of purine-nucleosides of DNA

2′‐Deoxyadenosine causes apoptotic cell death in a human colon carcinoma cell line

Contact Info

Product

Resources

About