Nitric-oxide dependent apoptosis in ovarian carcinoma cell lines

PB Lirk, MBa, FB Bodrogi, MB a, M Kargl, MB a, K Greiner, MD a, JW Rieder, MD a

Department of Anesthesiology and Critical Care Medicine, Leopold-Franzens University of Innsbruck, Innsbruck, Tyrol Austria

AIM Recent studies found alternating profiles of inducible nitric oxide synthase (iNOS) gene expression in the ovarian carcinoma cell lines OVCAR-3, HOC-7, and 2774 upon incubation with stimulating cytokines. Aim of the present study was to test the hypothesis whether nitric oxide synthesis by iNOS is correlated with apoptosis. METHODS NO-dependent apoptosis was detected by DNA fragmentation analysis and fluorescence activated cell sorter analysis (FACS). RESULTS Correlations between NO formation in response to interleukin-1&beta, tumor necrosis factor-&alpha and interferon-&gamma and apoptosis were observed. DNA fragmentation was most prominent in OVCAR-3 (34.1 +/- 1.8%) and HOC-7 (12.9 +/- 0.45%) and undetectable in 2774 (4.54 +/- 0.4%) cells. The rate of apoptosis correlated with NO synthesis. This effect was suppressed by addition of the selective iNOS inhibitor aminoguanidine. CONCLUSION In certain cell lines, the rate of NO synthesis is correlated with the degree of programmed cell death (apoptosis). This may, in part, explain the benefit of cytokine application in ovarian carcinoma patients, as documented for interferon-&gamma.

KEY WORDS: Inducible nitric oxide synthase (iNOS), apoptosis, ovarian carcinoma, interferon-&gamma.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Apoptosis - Molecular Mechanisms.