Affiliations: Department of Health Sciences, Faculty of Science,
University of Mauritius, Redúit, Mauritius. E-mail:
[email protected]
Abstract: Extracellular ATP (ATPo) and adenosine are cytotoxic to several
cancer cell lines, suggesting their potential use for anticancer therapy.
Adenosine causes cytotoxicity, either when added exogenously or when generated
from ATPo hydrolysis, via mechanisms which are not mutually exclusive and which
involve, adenosine receptor activation, pyrimidine starvation and/or increases
in intracellular S-adenosylhomocysteine: S-adenosylmethionine ratio. Given that
adenosine also appears to protect against cytotoxicity via mechanisms including
immunity against damage by oxygen free radicals, an understanding of the
contribution of adenosine to ATPo-induced cytotoxicity is thus crucial, when
considering any potential therapeutic use for these compounds. However, such an
understanding has been largely hindered by the fact that many studies have not
focused enough on the possibility that both ATPo and adenosine may mediate
cytotoxicity in the same system. Such studies can benefit from use a range of
ATPo concentrations when assessing the contribution of adenosine to
ATPo-induced cytotoxicity. Whilst future molecular and pharmacological studies
are needed to establish the nature of the cytotoxic adenosine receptor, it is
possible that more than just one adenosine receptor type is involved and that
the cytotoxic receptor(s) type is more likely to have a low affinity for
adenosine. Activation of the adenosine receptor(s) would thus lead to
cytotoxicity only at relatively high adenosine concentrations, while lower
adenosine concentrations mediate non-cytotoxic physiological effects.
