Nitric oxide-induced apoptosis in human pancreatic carcinoma cell lines is associated with a G1-arrest and an increase of the cyclin-dependent kinase inhibitor p21WAF1/CIP1.
Nitric oxide (NO) is a messenger molecule with various biological activities including DNA damage. In the present study, we examined the influence of endogenously produced NO on human pancreatic cell lines. In response to cytokine stimulation (tumor necrosis factor alpha, IFN-gamma, and interleukin 1beta), human pancreatic carcinoma cell lines expressed the inducible NO synthase that synthesizes NO, detectable as nitrate and nitrite in the culture supernatants. Endogenously produced NO induced apoptosis in all of the tested pancreatic carcinoma cell lines. In cell cycle analysis, endogenous production of NO revealed a G1-arrest in all of the tested cell lines. This G1-arrest was blockable by addition of NG-monomethyl-L-arginine. These data indicate that NO induces a G1-arrest followed by apoptosis in pancreatic carcinoma cell lines.
Department of General Surgery, University of Ulm, Germany.
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Gansauge
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Nussler
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HG
Beger
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Gansauge
D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis* / Q000235:genetics; D016193:G1 Phase / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D009566:Nitrates / Q000032:analysis; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000032:analysis; D015739:Nocodazole / Q000494:pharmacology; D009707:Nucleosomes / Q000378:metabolism; D010190:Pancreatic Neoplasms; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D019323:omega-N-Methylarginine / Q000494:pharmacology
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D007375:Interleukin-1; D009566:Nitrates; D009573:Nitrites; D009707:Nucleosomes; D014409:Tumor Necrosis Factor-alpha; D016159:Tumor Suppressor Protein p53; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D007371:Interferon-gamma; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D015739:Nocodazole