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Adenosine modulates cell proliferation in human colonic adenocarcinoma. I. Possible involvement of adenosine A1
V Lelièvre1, J M Muller, J Falcón
1Laboratoire de Biologie des Interactions Cellulaires, CNRS UMR 6558, Université de Poitiers, France.
Abstract:
Several lines of evidence suggest that extracellular adenosine interacting with specific cell surface receptors may influence cell growth and differentiation of cancer cells in culture. The data presented here demonstrate that various treatments of human colonic adenocarcinoma HT29 cells in the presence of exogenously added adenosine deaminase, which converts extracellular adenosine into inosine, resulted in a significant decrease of the proliferation. Cell growth inhibition was also observed in the presence of adenosine A1 receptor antagonists. These various treatments also induced a significant elevation of basal intracellular cAMP levels. This strongly indicated that extracellular adenosine was maintaining low intracellular cAMP levels in HT29 cells. A partial pharmacological characterization of the binding of the adenosine A1 receptor agonist [3H]CCPA (2-chloro-N6-cyclopentyl[2,3,4,5-(3)H]adenosine), and the adenosine A1 receptor antagonist [3H]DPCPX (cyclopentyl-1,3-dipropyl[2,3-(3)H]xanthine), to HT29 cells is also provided. Together the data support the idea that A1-adenosine receptors are expressed in HT29 cells and might mediate part of the above described effects of adenosine on cell proliferation.
Insights
Extracellular adenosine, interacting with adenosine A1 receptors, inhibits human colon cancer cell proliferation by increasing intracellular cAMP levels. This suggests A1-adenosine receptors play a role in regulating cancer cell growth.
Area of Science:
- Cell Biology
- Cancer Research
- Pharmacology
Background:
- Extracellular adenosine and its cell surface receptors are implicated in cancer cell growth and differentiation.
- Human colonic adenocarcinoma HT29 cells are a relevant model for studying colon cancer.
- Adenosine signaling pathways are complex and their role in specific cancer types requires further elucidation.
Purpose of the Study:
- To investigate the role of extracellular adenosine and adenosine A1 receptors in the proliferation of HT29 colon cancer cells.
- To determine the effect of modulating extracellular adenosine levels and A1 receptor activity on cancer cell growth.
- To characterize the expression and function of adenosine A1 receptors in HT29 cells.
Main Methods:
- Treatment of HT29 cells with adenosine deaminase to convert adenosine to inosine.
- Administration of adenosine A1 receptor antagonists.
- Measurement of intracellular cyclic adenosine monophosphate (cAMP) levels.
- Pharmacological characterization of [3H]CCPA and [3H]DPCPX binding to HT29 cells.
Main Results:
- Treatments reducing extracellular adenosine or blocking A1 receptors significantly decreased HT29 cell proliferation.
- These treatments led to a significant elevation of basal intracellular cAMP levels.
- Data indicate that extracellular adenosine normally maintains low intracellular cAMP levels in HT29 cells.
- Evidence supports the expression of functional adenosine A1 receptors on HT29 cells.
Conclusions:
- Extracellular adenosine, acting through A1-adenosine receptors, inhibits proliferation of HT29 colon cancer cells.
- Adenosine A1 receptor signaling in HT29 cells is linked to the regulation of intracellular cAMP levels.
- These findings suggest that targeting the adenosine A1 receptor pathway could be a potential therapeutic strategy for colon adenocarcinoma.