Isfahan University of Medical Sciences

Science Communicator Platform

Stay connected! Follow us on X network (Twitter):
Share this content! On (X network) By
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 Publisher Pubmed



Aghaei M1 ; Panjehpour M2, 4 ; Karamitehrani F1 ; Salami S3
Authors
Show Affiliations
Authors Affiliations
  1. 1. Department of Clinical Biochemistry, School of Medical Science, Tarbiat Modares University, Tehran, P.O. Box: 14115-331, Iran
  2. 2. Department of Clinical Biochemistry, School of Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran
  3. 3. Department of Biochemistry, School of Medical Science, Urmia University of Medical Sciences, Urmia, Iran
  4. 4. Bioinformatics Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

Source: Journal of Cancer Research and Clinical Oncology Published: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. © 2011 Springer-Verlag.
Related Docs
View other Related Docs
1. Adenosine Induces Cell-Cycle Arrest and Apoptosis in Androgen-Dependent And-Independent Prostate Cancer Cell Lines, Lncap-Fgc-10, Du-145, and Pc3, Prostate (2012)
2. Mitochondrial and Caspase Pathways Are Involved in the Induction of Apoptosis by Ib-Meca in Ovarian Cancer Cell Lines, Tumor Biology (2014)
3. Adenosine Induces Cell Cycle Arrest and Apoptosis Via Cyclind1/Cdk4 and Bcl-2/Bax Pathways in Human Ovarian Cancer Cell Line Ovcar-3, Tumor Biology (2013)
4. Activation of A2b Adenosine Receptor Regulates Ovarian Cancer Cell Growth: Involvement of Bax/Bcl-2 and Caspase-3, Biochemistry and Cell Biology (2015)
5. A3 Adenosine Receptor Agonist Induce G1 Cell Cycle Arrest Via Cyclin D and Cyclin-Dependent Kinase 4 Pathways in Ovcar-3 and Caov-4 Cell Lines, Journal of Cancer Research and Therapeutics (2017)
6. Adenosine Receptor Expression in Two Different Human Cancer Cell Lines at Molecular Level, Iranian Journal of Cancer Prevention (2010)
7. Expression of Adenosine Receptor Subclasses in Malignant and Adjacent Normal Human Prostate Tissues, Prostate (2015)
8. Molecular Expression of Adenosine Receptors in Ovcar-3, Caov-4 and Skov-3 Human Ovarian Cancer Cell Lines, Research in Pharmaceutical Sciences (2015)
Experts (# of related papers)
View all Related Experts
Mahmoud Aghaei (20)
Mojtaba Panjehpour (15)
Other Related Docs
9. Expression of A2a and A2b Adenosine Receptors in Human Breast Tumors, Journal of Isfahan Medical School (2011)
10. Expression of A1 and A3 Adenosine Receptors in Human Breast Tumors, Tumori (2012)
11. Investigation the Effect of Adenosine A1 Receptor Agonist and Antagonist on P53 Gene Expression, and Apoptosis Pathways and Rate in U87mg Multiform Glioblastoma, Journal of Isfahan Medical School (2021)
12. Evaluation of the Effects A2b Adenosine Receptor-Agonist (Bay 60–6583) in Induction of Apoptosis in Achn Renal Cancer Cell Line, Journal of Isfahan Medical School (2018)
13. Apoptosis and Cell Cycle Regulatory Effects of Adenosine by Modulation of Gli-1 and Erk1/2 Pathways in Cd44+ and Cd24− Breast Cancer Stem Cells, Cell Proliferation (2017)
14. Adenosine Modulates Cell Growth in the Human Breast Cancer Cells Via Adenosine Receptors, Oncology Research (2007)
15. Estrogen Stimulates Adenosine Receptor Expression Subtypes in Human Breast Cancer Mcf-7 Cell Line, Research in Pharmaceutical Sciences (2018)
16. Physiological Role of Adenosine and Its Receptors in Tissue Hypoxia-Induced Angiogenesis, Physiology and Pharmacology (2012)
17. A2b Adenosine Receptor Agonist Induces Cell Cycle Arrest and Apoptosis in Breast Cancer Stem Cells Via Erk1/2 Phosphorylation, Cellular Oncology (2018)
18. Inhibition of Phosphodiestrase 9 Induces Cgmp Accumulation and Apoptosis in Human Breast Cancer Cell Lines, Mcf-7 and Mda-Mb-468, Cell Proliferation (2012)
19. A3 Receptor Agonist, Cl-Ibmeca, Potentiate Glucose-Induced Insulin Secretion From Min6 Insulinoma Cells Possibly Through Transient Ca2+ Entry, Research in Pharmaceutical Sciences (2019)
20. The Effect of Adenosine A1 Receptor Agonist and Antagonist on P53 and Caspase 3, 8, and 9 Expression and Apoptosis Rate in Mcf-7 Breast Cancer Cell Line, Research in Pharmaceutical Sciences (2016)
21. Adenosine Protects Pancreatic Beta Cells Against Apoptosis Induced by Endoplasmic Reticulum Stress, Journal of Cellular Biochemistry (2019)
22. Exosomes As Efficient Platforms for Delivering Adenosine-Tetra Peptide Conjugate to Pancreatic Cancer Cells: An in Vitro/In Silico Study, Journal of Drug Delivery Science and Technology (2023)
23. Dihydroartemisinin Enhances the Therapeutic Efficacy of Bh3 Mimetic Inhibitor in Acute Lymphoblastic Leukemia Cells Via Inhibition of Mcl-1, Asian Pacific Journal of Cancer Prevention (2024)
24. Ipp-1 Controls Akt/Creb Phosphorylation Extension in A2a Adenosine Receptor Signaling Cascade in Min6 Pancreatic Β-Cell Line, European Journal of Pharmacology (2019)
25. The Effects of Abt-199 and Dihydroartemisinin Combination on Cell Growth and Apoptosis in Human U937 and Kg-1 Cancer Cells, Asian Pacific Journal of Cancer Prevention (2024)
26. Α2β1 Integrin Specific Inhibitor Btt-3033 Promotes Paclitaxel-Induced Apoptosis in Human Ovarian Cancer Cells, Research in Pharmaceutical Sciences (2024)
27. A3 Adenosine Receptor Agonist Inhibited Survival of Breast Cancer Stem Cells Via Gli-1 and Erk1/2 Pathway, Journal of Cellular Biochemistry (2017)
28. S100a8 Inhibition in Leukemic Lymphoblasts Induces Sensitivity to Chemotherapy and Inhibition of Disease Relapse, Medical Oncology (2022)
29. Belinostat Effects on Expression of Rbm5 Tumor Suppressor Gene and Inhibits Prostate Cancer Cell Line (Pc3) Proliferation, Electronic Journal of General Medicine (2018)
30. Formononetin and Dihydroartemisinin Act Synergistically to Induce Apoptosis in Human Acute Myeloid Leukemia Cell Lines, Cell Journal (2024)
31. Effect of Ascorbic Acid and Menthone on the Caspase 3 in the Sperm Cells of Acyclovir Treated Rats, Acta Medica Mediterranea (2016)
32. Mtdh/Aeg-1 Contributes to Central Features of the Neoplastic Phenotype in Bladder Cancer, Urologic Oncology: Seminars and Original Investigations (2014)
33. A2a Adenosine Receptor Agonist Improves Endoplasmic Reticulum Stress in Min6 Cell Line Through Protein Kinase A/ Protein Kinase B/ Cyclic Adenosine Monophosphate Response Element-Binding Protein/ and Growth Arrest and Dna-Damage-Inducible 34/ Eukaryotic Initiation Factor 2Α Pathways, Journal of Cellular Physiology (2019)
34. Phytochemical Analysis of Artemisia Kopetdaghensis: Sesquiterpene Lactones With Proapoptotic Activity Against Prostate Cancer Cells, Phytochemistry (2022)
35. Adenosine A1 Receptor Modifies P53 Expression and Apoptosis in Breast Cancer Cell Line Mcf-7, Bratislava Medical Journal (2016)
36. Dihydroartemisinin Induces Apoptosis in Human Bladder Cancer Cell Lines Through Reactive Oxygen Species, Mitochondrial Membrane Potential, and Cytochrome C Pathway, International Journal of Preventive Medicine (2017)
37. Mechanisms of Simvastatin Myotoxicity: The Role of Autophagy Flux Inhibition, European Journal of Pharmacology (2019)