Agmatine inhibits the proliferation of rat hepatoma cells by modulation of polyamine metabolism

Background/Aims: Previous experiments have shown that agmatine, the product of arginine decarboxylase, is transported in competition with putrescine into quiescent rat hepatocytes, where it promotes several effects, including marked decrease of intracellular polyamines and induction of apoptosis. Th...

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Published in:Journal of hepatology Vol. 39; no. 5; pp. 793 - 799
Main Authors: Gardini, Giulia, Cravanzola, Carlo, Autelli, Riccardo, Testore, Giovanni, Cesa, Roberta, Morando, Laura, Solinas, Sandro Paolo, Muzio, Giuliana, Grillo, Maria Angelica, Colombatto, Sebastiano
Format: Journal Article
Language:English
Published: Netherlands Elsevier B.V 01.11.2003
Subjects:
Actins - metabolism
Agmatine
Agmatine - administration & dosage
Agmatine - pharmacology
Animals
Carcinoma, Hepatocellular - metabolism
Carcinoma, Hepatocellular - pathology
Carcinoma, Hepatocellular - ultrastructure
Cell Division - drug effects
Cell Line, Tumor
Cytoskeleton - metabolism
Cytoskeleton - ultrastructure
Dose-Response Relationship, Drug
G2 Phase
Hepatoma cell
Immunohistochemistry - methods
Liver Neoplasms - metabolism
Liver Neoplasms - pathology
Liver Neoplasms - ultrastructure
Microscopy, Electron
Mitosis
Polyamine
Polyamines - antagonists & inhibitors
Rats
Staining and Labeling
Tubulin - metabolism
Hepatoma cell
Agmatine
Polyamine
ISSN:0168-8278, 1600-0641
Online Access:Get full text
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Summary:Background/Aims: Previous experiments have shown that agmatine, the product of arginine decarboxylase, is transported in competition with putrescine into quiescent rat hepatocytes, where it promotes several effects, including marked decrease of intracellular polyamines and induction of apoptosis. The primary aim of the present study was to assess the action of agmatine on transformed and proliferating hepatic rat cells. Methods: To assess the effect of agmatine on hepatoma cells, analysis by flow cytometry, Western blotting, reverse transcription–polymerase chain reaction, scanning and transmission electron microscopy, immunofluorescence detection of β-actin and α-tubulin were performed. Results: The results showed that agmatine has antiproliferative effects on the cell lines studied (HTC, JM2, HepG2). Further experiments were performed on HTC cells. The effect was proportional to agmatine concentration (in a range between 50 and 500 μM). It was not correlated with induction of necrosis or apoptosis and was accompanied by accumulation in G 2/M cell cycle phase and by dramatic modification of cell morphology. Spermidine reversed these effects, suggesting that the marked decrease of the polyamine pool is the main target of agmatine. Conclusions: The results obtained show a relationship between the decrease of intracellular polyamine content, the rate of cell growth and the cytoskeleton organization.
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ISSN:0168-8278
1600-0641
DOI:10.1016/S0168-8278(03)00386-6