Iron depletion decreases cancer growth

Modulation of cell proliferation and polyamine metabolism in rat liver
cell cultures by the iron chelator O-trensox
Authors: Gaboriau, François; Laupen-Chassay, Cindy; Pasdeloup, Nicole;
Pierre, Jean-Louis; Brissot, Pierre; Lescoat, Gérard1

Source: BioMetals, Volume 19, Number 6, December 2006, pp. 623-632(10)

Publisher: Springer

Abstract:

The antiproliferative effects of the iron chelator O-trensox and the
ornithine-decarboxylase (ODC) inhibitor alpha-difluoromethylornithine
(DFMO) were characterized in the rat hepatoma cell line FAO, the rat
liver epithelial cell line (RLEC) and the primary rat hepatocyte
cultures stimulated by EGF. We observed that O-trensox and DFMO
decreased cell viabilty and DNA replication in the three culture
models. The cytostatic effect of O-trensox was correlated to a
cytotoxicity, higher than for DFMO, and to a cell cycle arrest in G0/
G1 or S phases. Moreover, O-trensox and DFMO decreased the
intracellular concentration of spermidine in the three models without
changing significantly the spermine level. We concluded that iron, but
also polyamine depletion, decrease cell growth. However, the drop in
cell proliferation obtained with O-trensox was stronger compared to
DFMO effect. Altogether, our data provide insights that, in the three
rat liver cell culture models, the cytostatic effect of the iron
chelator O-trensox may be the addition of two mechanisms: iron and
polyamine depletion.
Keywords: cell proliferation; iron chelator; polyamines; rat liver
cells

Document Type: Research article

DOI: 10.1007/s10534-006-6888-y

Affiliations: 1: Email: gerard.lescoat@rennes.inserm.fr


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