Abstract | BACKGROUND/AIMS: METHODS: RESULTS: Contrary to the expected results, we have found that pancreastatin inhibits protein and DNA synthesis in HTC hepatoma cells. On the other hand, when the activity of NO synthase was inhibited by N-monomethyl- L-arginine (NMLA), the inhibitory effect of pancreastatin on DNA and protein synthesis was not only reverted, but a dose-dependent stimulatory effect was observed, probably due to MAPK activation, since it was prevented by PD98059. These data strongly suggested the role of NO in the inhibitory effect of pancreastatin on protein and DNA synthesis, which is overcoming the effect on MAPK activation. Moreover, pancreastatin dose-dependently increased NO production in parallel to cyclic guanosine monophosphate (cGMP). Both effects were prevented by NMLA. Finally, an indirect effect of pancreastatin through the induction of apoptosis was ruled out. CONCLUSIONS: Therefore, the NO and the cGMP produced by the NO-activated guanylate cyclase may mediate the dose-dependent inhibitory effect of pancreastatin on growth and proliferation in HTC hepatoma cells.
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Authors | V Sánchez-Margalet, C González-Yanes, S Najib |
Journal | Journal of hepatology
(J Hepatol)
Vol. 35
Issue 1
Pg. 80-5
(Jul 2001)
ISSN: 0168-8278 [Print] Netherlands |
PMID | 11495046
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Chromogranin A
- Chromogranins
- Enzyme Inhibitors
- Pancreatic Hormones
- Protein Synthesis Inhibitors
- chromogranin A, rat
- pancreastatin
- omega-N-Methylarginine
- Nitric Oxide
- DNA
- Cyclic GMP
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Topics |
- Animals
- Carcinoma, Hepatocellular
(genetics, metabolism, pathology)
- Cell Division
(drug effects)
- Chromogranin A
- Chromogranins
- Cyclic GMP
(biosynthesis)
- DNA
(antagonists & inhibitors, biosynthesis)
- Dose-Response Relationship, Drug
- Enzyme Inhibitors
(pharmacology)
- Liver Neoplasms
(genetics, metabolism, pathology)
- Nitric Oxide
(antagonists & inhibitors, biosynthesis)
- Pancreatic Hormones
(chemistry, pharmacology)
- Protein Synthesis Inhibitors
(pharmacology)
- Rats
- Tumor Cells, Cultured
- omega-N-Methylarginine
(pharmacology)
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