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Mechanisms of adenosine-induced cytotoxicity and their clinical and physiological implications

Sharmila P Seetulsingh-Goorah1

  • 1Department of Health Sciences, Faculty of Science, University of Mauritius, Redúit, Mauritius. seetulg@uom.ac.mu

Biofactors (Oxford, England)
|October 3, 2006
PubMed

Insights

Extracellular ATP (ATPo) and adenosine show potential as anticancer therapies by inducing cancer cell death. Understanding adenosine

Area of Science:

  • Biochemistry
  • Pharmacology
  • Cancer Biology

Background:

  • Extracellular ATP (ATPo) and adenosine exhibit cytotoxic effects on various cancer cell lines, indicating therapeutic potential.
  • Adenosine-induced cytotoxicity can occur through exogenous administration or ATPo hydrolysis, involving adenosine receptor activation, pyrimidine starvation, and altered S-adenosylhomocysteine/S-adenosylmethionine ratios.
  • Adenosine may also confer protection against cytotoxicity via antioxidant mechanisms, complicating its role in ATPo-induced cell death.

Purpose of the Study:

  • To elucidate the contribution of adenosine to ATPo-induced cytotoxicity in cancer cells.
  • To address the challenge of distinguishing the independent and combined effects of ATPo and adenosine in cytotoxic mechanisms.
  • To investigate the characteristics of adenosine receptors involved in cytotoxicity.

Main Methods:

  • Utilized a range of ATPo concentrations to assess adenosine's contribution to cytotoxicity.
  • Examined mechanisms including adenosine receptor activation, pyrimidine metabolism, and S-adenosylhomocysteine/S-adenosylmethionine ratios.
  • Considered potential involvement of multiple adenosine receptor subtypes with varying affinities.

Main Results:

  • Adenosine contributes to ATPo-induced cytotoxicity through multiple pathways.
  • Cytotoxic adenosine receptor activation likely requires relatively high adenosine concentrations, suggesting a low-affinity receptor.
  • Lower adenosine concentrations may mediate physiological effects rather than cytotoxicity.

Conclusions:

  • A comprehensive understanding of adenosine's role in ATPo-induced cytotoxicity is critical for developing effective anticancer therapies.
  • Future molecular and pharmacological studies are necessary to identify the specific cytotoxic adenosine receptor(s).
  • The identified cytotoxic adenosine receptor(s) may exhibit low affinity, mediating cell death only at elevated adenosine levels.

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