Adenosine induces cell-cycle arrest and apoptosis in androgen-dependent and-independent prostate cancer cell lines, LNcap-FGC-10, DU-145, and PC3

Adenosine has been shown to inhibit cell growth and induce apoptosis in
the several cancer cells via intrinsic and extrinsic pathway. The present study was designed
to understand the mechanism underlying adenosine-induced apoptosis in the DU-145, PC3,
and LNcap-FGC10 human prostate cancer cells.
METHODS. To observe cell viability and proliferation, MTT assay, cell counting, and BrdU
assay were carried out in DU-145, PC3, and LNcap-FGC10 cells. Apoptosis was assessed
with the analysis of cell cycle, Hoechst 33258 staining, propidium iodide and annexin-V staining,
reactive oxygen species (ROS) formation, mitochondrial membrane potential (DCM)
measurement, caspase-3 activity assay, Bcl-2 and Bax protein expression. Moreover, the
expression of adenosine receptors and the effects of adenosine receptor (A1, A2a, and A3)
antagonists were examined.
RESULT. Adenosine significantly reduced cell proliferation in a dose-dependent manner in
DU-145, PC3, and LNcap-FGC10 cell lines. Adenosine induced arrest in the cell-cycle progression
in G0/G1 phase through Cdk4/cyclinD1-mediated pathway. Adenosine induced
apoptosis, which was determined by morphological changes and increased sub-G1 population.
Furthermore, increase of ROS, loss of MMP, activation of caspase-3, and down-regulation
of Bcl-2 expression was observed. A1, A2a, A2b, and A3 adenosine receptors mRNA are
expressed in the cell lines. Moreover, adenosine-induced apoptosis was inhibited by
MRS1220, A3 adenosine receptor antagonist.
CONCLUSION. Our results suggest that adenosine induced apoptosis in prostate cancer
cells via the mitochondrial pathway and is related to the adenosine receptors. These data
might suggest that adenosine could be used as an agent for the treatment of prostate cancer