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Adenosine induces cell cycle arrest and apoptosis via cyclinD1/Cdk4 and Bcl-2/Bax pathways in human ovarian cancer cell line OVCAR-3

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Tumor Biology

Abstract

Adenosine is a regulatory molecule with widespread physiological effects in almost every cells and acts as a potent regulator of cell growth. Adenosine has been shown to inhibit cell growth and induce apoptosis in the several cancer cells via caspase activation and Bcl-2/Bax pathway. The present study was designed to understand the mechanism underlying adenosine-induced apoptosis in the OVCAR-3 human ovarian cancer cells. MTT viability, BrdU and cell counting assays were used to study the cell proliferation effect of adenosine in presence of adenosine deaminase inhibitor and the nucleoside transporter inhibitor. Cell cycle analysis, propidium iodide and annexin V staining, caspase-3 activity assay, cyclinD1, Cdk4, Bcl-2 and Bax protein expressions were assessed to detect apoptosis. Adenosine significantly inhibited cell proliferation in a concentration-dependent manner in OVCAR-3 cell line. Adenosine induced cell cycle arrest in G0/G1 phase via Cdk4/cyclinD1-mediated pathway. Adenosine induced apoptosis, which was determined by Annexin V-FITC staining and increased sub-G1 population. Moreover, down-regulation of Bcl-2 protein expression, up-regulation of Bax protein expression and activation of caspase-3 were observed in response to adenosine treatment. The results of this study suggest that extracellular adenosine induced G1 cell cycle arrest and apoptosis in ovarian cancer cells via cyclinD1/ Cdk4 and Bcl-2/Bax pathways and caspase-3 activation. These data might suggest that adenosine could be used as an agent for the treatment of ovarian cancer.

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Acknowledgment

This work was supported by a grant from Chalous Branch, Islamic Azad University, Chalous, Iran.

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Authors and Affiliations

  1. Department of Laboratory Sciences, Chalous Branch, Islamic Azad University, Chalous, Iran

    Saeid Shirali

  2. Department of Clinical Biochemistry, School of Pharmacy and Isfahan Pharmaceutical Sciences Research Center, Isfahan University of Medical Sciences, P.O. Box 81746-73461, Isfahan, Iran

    Mahmoud Aghaei

  3. Department of Antibody and Antigen Engendering, Monoclonal Antibody Research Center, Avicenna Research Institute, Academic Center for Education, Culture and Research (ACECR), Tehran, Iran

    Mahdi Shabani

  4. Department of Clinical Biochemistry, School of Medical Science, Tarbiat Modares University, Tehran, Iran

    Mojtaba Fathi & Marzieh Moeinifard

  5. Department of Bacteriology, School of Medical Science, Tarbiat Modares University, Tehran, Iran

    Majid Sohrabi

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  1. Saeid Shirali
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  2. Mahmoud Aghaei
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  3. Mahdi Shabani
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  4. Mojtaba Fathi
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Correspondence to Mahmoud Aghaei.

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Shirali, S., Aghaei, M., Shabani, M. et al. Adenosine induces cell cycle arrest and apoptosis via cyclinD1/Cdk4 and Bcl-2/Bax pathways in human ovarian cancer cell line OVCAR-3. Tumor Biol. 34, 1085–1095 (2013). https://doi.org/10.1007/s13277-013-0650-1

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  • DOI: https://doi.org/10.1007/s13277-013-0650-1

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