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Journal of Cancer Research and Clinical Oncology

Published in:

01-10-2011 | Original Paper

Molecular mechanisms of A3 adenosine receptor-induced G1 cell cycle arrest and apoptosis in androgen-dependent and independent prostate cancer cell lines: involvement of intrinsic pathway

Authors: Mahmoud Aghaei, Mojtaba Panjehpour, Fatemeh Karami-Tehrani, Siamak Salami

Published in: Journal of Cancer Research and Clinical Oncology | Issue 10/2011

Abstract

Purpose

A3 adenosine receptor has shown several physiological and pathological activities, including cell proliferation and apoptosis in various cancer cell lines. This study is designed to investigate molecular mechanism and apoptotic pathway of A3 adenosine receptor in DU-145, PC3 and LNcap-FGC10 human prostate cancer cells.

Methods

The expression level of A3 adenosine receptor was examined using real-time RT-PCR. cAMP concentration was also measured. MTT viability, cell counting and BrdU incorporation tests were used to study the cell proliferation effect of IB-MECA. Cell cycle analysis, Annexin V-FITC staining, Hoechst 33258 staining, mitochondrial membrane potential (ΔΨM), caspase-3 activity, Bcl-2 and Bax protein expression were used to detect apoptosis.

Result

A3 adenosine receptors mRNAs were detected at different levels. IB-MECA inhibited forskolin-stimulated cAMP. IB-MECA at (1 μM) suppressed cell proliferation and induced G1 cell cycle arrest. Indeed, IB-MECA down-regulated the expression of CDK4, cyclin D1 and up-regulated p53 expression. IB-MECA at (10–100 μM) induced apoptosis. The activity of caspase-3 was also increased. Expression of Bcl-2 was decreased in response to IB-MECA, while the expression of Bax protein was increased. The results showed a significant loss of ΔΨM, in a dose-dependent manner.

Conclusion

This study introduces a possible mechanism through A3 adenosine receptor activation. IB-MECA inhibited prostate cancer cells proliferation and induced G1 cell cycle arrest through p53, Cdk4/cyclinD1 pathway. Apoptosis determined by characteristic morphological changes and increased in sub-G1 population. Loss of MMP, activation of caspase-3 and down-regulation of Bcl-2 expression indicated mitochondrial signaling pathway that involved in the apoptosis.

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Title: Molecular mechanisms of A3 adenosine receptor-induced G1 cell cycle arrest and apoptosis in androgen-dependent and independent prostate cancer cell lines: involvement of intrinsic pathway
Authors: Mahmoud Aghaei
Mojtaba Panjehpour
Fatemeh Karami-Tehrani
Siamak Salami
Publication date: 01-10-2011
Publisher: Springer-Verlag
Published in: Journal of Cancer Research and Clinical Oncology / Issue 10/2011
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-011-1031-z

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