Intestinal tumor and agmatine (decarboxylated arginine): low content in colon carcinoma tissue specimens and inhibitory effect on tumor cell proliferation in vitro.
BACKGROUND
The polyamine system is a promising target for anticancer therapy. Ideally, an antineoplastic compound affecting this system should inhibit both ornithine decarboxylase and the polyamine transporter, and toxicity should be mild. Agmatine, decarboxylated L-arginine, appears to be such a compound.


METHODS
Adenosine triphosphate levels and the protein content of cell populations in culture were identified as surrogate markers for cell count. Agmatine content in cells and tissue specimens was measured by high-performance liquid chromatography. Antizyme levels were estimated by Western blotting.


RESULTS
Agmatine inhibited the proliferation of six human intestinal tumor cell lines in a concentration-dependent manner; this inhibition probably was attributable to an interaction between agmatine and the intracellular polyamine system. Consistent with the inverse relation between cell proliferation and agmatine concentration was the finding that agmatine content in human colon carcinoma tissue was approximately one-half as great as it was in adjacent macroscopically normal tissue.


CONCLUSIONS
The results of the current study were compatible with the hypothesis that agmatine possesses antineoplastic action against intestinal tumor cells. It is likely that this activity is attributable to agmatine's regulatory role in polyamine homeostasis.
Institute of Pharmacology and Toxicology, University of Bonn, Bonn, Germany. molderings@uni-bonn.de
Gerhard J
GJ
Molderings
Bettina
B
Kribben
Anja
A
Heinen
Detlev
D
Schröder
Michael
M
Brüss
Manfred
M
Göthert
D000255:Adenosine Triphosphate / Q000032:analysis; D000376:Agmatine / Q000032:analysis* / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007414:Intestinal Neoplasms / Q000473:pathology*; D009955:Ornithine Decarboxylase / Q000378:metabolism; D011073:Polyamines / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D011073:Polyamines; D000376:Agmatine; D000255:Adenosine Triphosphate; D009955:Ornithine Decarboxylase