Benzamide riboside induces apoptosis independent of Cdc25A expression in human ovarian carcinoma N.1 cells - Cell Death & Differentiation
- ️Jayaram, Hiremagalur N
- ️Fri Aug 27 1999
Abstract
One of the mechanisms of action of a new oncolytic agent, benzamide riboside (BR) is by inhibiting inosine 5′-monophosphate dehydrogenase (IMPDH) which catalyzes the formation of xanthine 5′-monophosphate from inosine 5′-monophosphate and nicotinamide adenine dinucleotide, thereby restricting the biosynthesis of guanylates. In the present study BR (10–20 μM) induced apoptosis in a human ovarian carcinoma N.1 cell line (a monoclonal derivative of its heterogenous parent line HOC-7). This was ascertained by DNA fragmentation, TUNEL assay, [poly(ADP)ribose polymerase]-cleavage and alteration in cell morphology. Apoptosis was accompanied by sustained c-Myc expression, concurrent down-regulation of cdc25A mRNA and protein, and by inhibition of Cdk2 activity. Both Cdk2 and cdc25A are G1 phase specific genes and Cdk2 is the target of Cdc25A. These studies demonstrate that BR exhibits dual mechanisms of action, first by inhibiting IMPDH, and second by inducing apoptosis, which is associated with repression of components of the cell cycle that are downstream of constitutive c-Myc expression.
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Institute of Clinical Pathology, University of Vienna, Währinger Gürtel 18-20, Vienna, A-1090, Austria
Michael Grusch, Georg Rosenberger, Gerhard Fuhrmann, Birgit Titscher, Georg Oberhuber & Georg Krupitza
Department of Prenatal Diagnostic, Institute of Gynecology and Obstetrics, University of Vienna, Währinger Gürtel 18-20, Vienna, A-1090, Austria
Katja Braun & Markus Hengstschlaeger
Clinical Institute of Medical and Chemical Laboratory Diagnostics, University of Vienna, Währinger Gürtel 18-20, Vienna, A-1090, Austria
Thomas Szekeres & Monika Fritzer-Skekeres
Division of Organic Chemistry, Universität Gesamthochschule Paderborn, Paderborn, 1621-4790, Germany
Karsten Krohn
Laboratory of Experimental Oncology, Indiana University School of Medicine, Indianapolis, 46202-5119, IN, USA
Hiremagalur N Jayaram
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, 46202-5119, IN, USA
Hiremagalur N Jayaram
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- Michael Grusch
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- Georg Rosenberger
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- Gerhard Fuhrmann
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- Katja Braun
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- Birgit Titscher
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- Thomas Szekeres
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- Monika Fritzer-Skekeres
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- Georg Oberhuber
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- Karsten Krohn
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- Markus Hengstschlaeger
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- Georg Krupitza
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- Hiremagalur N Jayaram
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Correspondence to Hiremagalur N Jayaram.
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Grusch, M., Rosenberger, G., Fuhrmann, G. et al. Benzamide riboside induces apoptosis independent of Cdc25A expression in human ovarian carcinoma N.1 cells. Cell Death Differ 6, 736–744 (1999). https://doi.org/10.1038/sj.cdd.4400546
Received: 28 December 1998
Revised: 22 April 1999
Accepted: 20 May 1999
Published: 27 August 1999
Issue Date: 01 August 1999
DOI: https://doi.org/10.1038/sj.cdd.4400546