Benzamide riboside induces apoptosis independent of Cdc25A expression in human ovarian carcinoma N.1 cells

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Benzamide riboside induces apoptosis independent of Cdc25A expression in human ovarian carcinoma N.1 cells. / Grusch, M; Rosenberger, G; Fuhrmann, G; Braun, K; Titscher, B; Szekeres, T; Fritzer-Skekeres, M; Oberhuber, G; Krohn, K; Hengstschlaeger, M; Krupitza, G; Jayaram, H N.

In: CELL DEATH DIFFER, Vol. 6, No. 8, 01.08.1999, p. 736-44.

Research output: SCORING: Contribution to journalSCORING: Journal articleResearchpeer-review

Harvard

Grusch, M, Rosenberger, G, Fuhrmann, G, Braun, K, Titscher, B, Szekeres, T, Fritzer-Skekeres, M, Oberhuber, G, Krohn, K, Hengstschlaeger, M, Krupitza, G & Jayaram, HN 1999, 'Benzamide riboside induces apoptosis independent of Cdc25A expression in human ovarian carcinoma N.1 cells', CELL DEATH DIFFER, vol. 6, no. 8, pp. 736-44. https://doi.org/10.1038/sj.cdd.4400546

APA

Grusch, M., Rosenberger, G., Fuhrmann, G., Braun, K., Titscher, B., Szekeres, T., Fritzer-Skekeres, M., Oberhuber, G., Krohn, K., Hengstschlaeger, M., Krupitza, G., & Jayaram, H. N. (1999). Benzamide riboside induces apoptosis independent of Cdc25A expression in human ovarian carcinoma N.1 cells. CELL DEATH DIFFER, 6(8), 736-44. https://doi.org/10.1038/sj.cdd.4400546

Vancouver

Bibtex

@article{7147b7df2e7e412da3e8d8378674d3a8,
title = "Benzamide riboside induces apoptosis independent of Cdc25A expression in human ovarian carcinoma N.1 cells",
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 microM) 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.",
keywords = "Adenocarcinoma, Apoptosis, Cell Division, Dose-Response Relationship, Drug, Enzyme Inhibitors, Female, Humans, IMP Dehydrogenase, Nucleosides, Ovarian Neoplasms, Tumor Cells, Cultured, cdc25 Phosphatases",
author = "M Grusch and G Rosenberger and G Fuhrmann and K Braun and B Titscher and T Szekeres and M Fritzer-Skekeres and G Oberhuber and K Krohn and M Hengstschlaeger and G Krupitza and Jayaram, {H N}",
year = "1999",
month = aug,
day = "1",
doi = "10.1038/sj.cdd.4400546",
language = "English",
volume = "6",
pages = "736--44",
journal = "CELL DEATH DIFFER",
issn = "1350-9047",
publisher = "NATURE PUBLISHING GROUP",
number = "8",

}

RIS

TY - JOUR

T1 - Benzamide riboside induces apoptosis independent of Cdc25A expression in human ovarian carcinoma N.1 cells

AU - Grusch, M

AU - Rosenberger, G

AU - Fuhrmann, G

AU - Braun, K

AU - Titscher, B

AU - Szekeres, T

AU - Fritzer-Skekeres, M

AU - Oberhuber, G

AU - Krohn, K

AU - Hengstschlaeger, M

AU - Krupitza, G

AU - Jayaram, H N

PY - 1999/8/1

Y1 - 1999/8/1

N2 - 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 microM) 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.

AB - 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 microM) 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.

KW - Adenocarcinoma

KW - Apoptosis

KW - Cell Division

KW - Dose-Response Relationship, Drug

KW - Enzyme Inhibitors

KW - Female

KW - Humans

KW - IMP Dehydrogenase

KW - Nucleosides

KW - Ovarian Neoplasms

KW - Tumor Cells, Cultured

KW - cdc25 Phosphatases

U2 - 10.1038/sj.cdd.4400546

DO - 10.1038/sj.cdd.4400546

M3 - SCORING: Journal article

C2 - 10467347

VL - 6

SP - 736

EP - 744

JO - CELL DEATH DIFFER

JF - CELL DEATH DIFFER

SN - 1350-9047

IS - 8

ER -