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

Aghaei, M and Karami Tehrani, F and Panjehpour, M and Salami, S and Fallahian, F (2012) Adenosine induces cell-cycle arrest and apoptosis in androgen-dependent and-independent prostate cancer cell lines, LNcap-FGC-10, DU-145, and PC3. Prostate, 72 (4). pp. 361-375.

Preview

Text 21438_ftp.pdf Download (1MB) | Preview

Abstract

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

Actions (login required)

View Item