2’-Deoxyadenosine causes apoptotic cell death in a human colon carcinoma cell line

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.