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Adenosine and deoxyadenosine induces apoptosis in oestrogen receptor-positive and -negative human breast cancer cells via the intrinsic pathway
Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.
Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modarres University, Tehran, Iran.
Department of Biochemistry and Medical Genetics, Manitoba Institute of Cell Biology, Cancer Care Manitoba, Winnipeg, Manitoba, Canada; Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.
Manitoba Institute of Cell Biology, Cancer Care Manitoba; Department of Biochemistry and Medical Genetics,University of Manitoba, Winnipeg, Canada .
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2005 (English)In: Cell Proliferation, ISSN 0960-7722, E-ISSN 1365-2184, Vol. 38, no 5, 269-285 p.Article in journal (Refereed) Published
Abstract [en]

In this study we have examined the cytotoxic effects of different concentrations of adenosine (Ado) and deoxyadenosine (dAdo) on human breast cancer cell lines. Ado and dAdo alone had little effect on cell cytotoxicity. However, in the presence of adenosine deaminase (ADA) inhibitor, EHNA, adenosine and deoxyadenosine led to significant growth inhibition of cells of the lines tested. Ado/EHNA and dAdo/EHNA-induced cell death was significantly inhibited by NBTI, an inhibitor of nucleoside transport, and 5'-amino-5'-deoxyadenosine, an inhibitor of adenosine kinase, but the effects were not affected by 8-phenyltheophylline, a broad inhibitor of adenosine receptors. The Ado/EHNA combination brought about morphological changes consistent with apoptosis. Caspase-9 activation was observed in MCF-7 and MDA-MB468 human breast cancer cell lines on treatment with Ado/EHNA or dAdo/EHNA, but, as expected, caspase-3 activation was only observed in MDA-MB468 cells. The results of the study, thus, suggest that extracellular adenosine and deoxyadenosine induce apoptosis in both oestrogen receptor-positive (MCF-7) and also oestrogen receptor-negative (MDA-MB468) human breast cancer cells by its uptake into the cells and conversion to AMP (dAMP) followed by activation of nucleoside kinase, and finally by the activation of the mitochondrial/intrinsic apoptotic pathway.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2005. Vol. 38, no 5, 269-285 p.
Keyword [en]
a(3) receptor, activation, caspases, central-nervous-system, cytochrome-c, death, extracellular atp, induced growth, nucleotides stimulate proliferation, smooth-muscle-cells
National Category
Cancer and Oncology Biochemistry and Molecular Biology Genetics
Identifiers
URN: urn:nbn:se:liu:diva-86996DOI: 10.1111/j.1365-2184.2005.00349.xISI: 000232305000001OAI: oai:DiVA.org:liu-86996DiVA: diva2:584185
Available from: 2013-01-08 Created: 2013-01-08 Last updated: 2017-12-06

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Los, Marek Jan

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