Nitric oxide-dependent apoptosis in ovarian carcinoma cell lines.
OBJECTIVE
In a recent study, we found different profiles of inducible nitric oxide synthase (iNOS) gene expression in the ovarian carcinoma cell lines OVCAR-3, HOC-7, and 2774 following stimulation by proinflammatory cytokines. The present study was performed to determine whether nitric oxide (NO) synthesis correlates with programmed cell death in these cells.


METHODS
NO-Dependent apoptosis was detected by DNA fragmentation analysis and fluorescence-activated cell sorter analysis.


RESULTS
NO formation in response to interferon gamma (IFN-gamma), interleukin-1beta (IL-1beta), and tumor necrosis factor alpha (TNF-alpha) was correlated with programmed cell death in the investigated cells. DNA fragmentation was most prominent in OVCAR-3 (34.17 +/- 1.81%), less pronounced in HOC-7 (12.86 +/- 0.45%), and undetectable in 2774 (4.54 +/- 0.40%) cells. The rate of apoptosis correlated with the amount of NO formation in cytokine-treated cells. Moreover, coincubation of OVCAR-3 and HOC-7 with the specific iNOS inhibitor aminoguanidine suppressed apoptosis induced by IFN-gamma, IL-1beta, and TNF-alpha.


CONCLUSIONS
Our data indicate that in OVCAR-3 and HOC-7 cells, NO synthesis induced by IFN-gamma, IL-1beta, and TNF-alpha is correlated with the degree of apoptotic cell death. In clinical situations, this might in part explain the benefit of cytokine application in ovarian carcinoma patients (e.g., documented for IFN-gamma).
Rieder
J
J
Department of Anesthesia and Critical Care Medicine, Department of Obstetrics and Gynecology, University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria.
Jahnke
R
R
Schloesser
M
M
Seibel
M
M
Czechowski
M
M
Marth
C
C
Hoffmann
G
G
D017209:Apoptosis; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D007375:Interleukin-1; D009566:Nitrates; D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D007371:Interferon-gamma