Antiproliferative and apoptotic effects in rat and human hepatoma cell cultures of the orally active iron chelator ICL670 compared to CP20: a possible relationship with polyamine metabolism

@article{Lescoat2007AntiproliferativeAA,
  title={Antiproliferative and apoptotic effects in rat and human hepatoma cell cultures of the orally active iron chelator ICL670 compared to CP20: a possible relationship with polyamine metabolism},
  author={G. Lescoat and K. Chantrel-Groussard and N. Pasdeloup and H. Nick and P. Brissot and F. Gaboriau},
  journal={Cell Proliferation},
  year={2007},
  volume={40}
}
Abstract.  Objective: Iron loading has been observed to have a hyperproliferative effect on hepatocytes in vitro and on tumour cells in vivo; removal of this iron being required to induce antitumour activity. Material and Methods: Antiproliferative effects of orally active tridentate iron chelator ICL670 (deferasirox) and bidentate iron chelator CP20 (deferiprone), mediated through the chelation of intracellular iron, were compared in rat hepatoma cell line FAO and human hepatoma cell line HUH7… Expand
Effects of deferasirox and deferiprone on cellular iron load in the human hepatoma cell line HepaRG
TLDR
The effects of CP20 suggest the potential involvement of this compound in the iron uptake from the external medium into the hepatocytes from the HepaRG cell line, therefore acting like a siderophore in this cell model. Expand
The Iron Chelator, Deferasirox, as a Novel Strategy for Cancer Treatment: Oral Activity Against Human Lung Tumor Xenografts and Molecular Mechanism of Action
TLDR
It is demonstrated that deferasirox is an orally effective antitumor agent against solid tumors. Expand
Effects of oral iron chelator deferasirox on human malignant lymphoma cells
TLDR
It is demonstrated that deferasirox, a new oral iron-chelating agent, induced early apoptosis in human malignant lymphoma cells, and this apoptotic effect is dependent on the caspase-3/caspases-9 pathway. Expand
Deferasirox shows in vitro and in vivo antileukemic effects on murine leukemic cell lines regardless of iron status.
TLDR
This study indicates an antileukemic effect of DFX regardless of iron status and suggests that the use of D FX has a survival benefit for SIO leukemia murine model in terms of iron chelation and antileukesmic therapy. Expand
Antiproliferative effect on HepaRG cell cultures of new calix[4]arenes
TLDR
The synthesis of new synthetic calix[4]arene podands bearing alkyl acid andAlkyl ester groups at the lower rim, designed as potential iron chelators are presented, and it is shown that novel substituted Calix[ 4]arenes could open the way to new valuable medicinal chemistry scaffolding. Expand
Quilamine HQ1-44, an iron chelator vectorized toward tumor cells by the polyamine transport system, inhibits HCT116 tumor growth without adverse effect.
TLDR
In vivo, in xenografted athymic nude mice, it is found that HQ1-44 was as effective as cis-platin in reducing HCT116 tumor growth, without its side effects, and as suggested by in vitro data, the depletion in exogenous or endogenous polyamines, known to activate the PTS, dramatically enhanced the antitumor efficiency of HQ 1-44. Expand
Antiproliferative and iron chelating efficiency of the new bis-8-hydroxyquinoline benzylamine chelator S1 in hepatocyte cultures.
TLDR
The results suggest that molecules such as S1 may constitute a promising starting point to improve cancer treatment and the iron chelating efficiency of S1 could explain at least partially its higher anti-proliferative effect compared to O-trensox. Expand
The Iron Chelator, Dp44mT, Effectively Inhibits Human Oral Squamous Cell Carcinoma Cell Growth in Vitro and in Vivo
TLDR
It is shown that iron chelators (Dp44mT, desferrioxamine (DFO), and deferasirox) all significantly inhibit SAS cell growth, and NDRG3 is a tumor suppressor gene in OSCC cells, and Dp 44mT could be a promising therapeutic agent for OSCC treatment. Expand
Ethanol effect on cell proliferation in the human hepatoma HepaRG cell line: relationship with iron metabolism.
TLDR
Ethanol-induced iron metabolism dysfunction could be one of the underlying mechanisms of ethanol antiproliferative effect and exogenous iron may accentuate ethanol hepatoxicity, and data suggest that iron metabolism manipulation by chelators may be a useful therapeutic approach in alcohol-related liver diseases. Expand
The oral iron chelator deferasirox represses signaling through the mTOR in myeloid leukemia cells by enhancing expression of REDD1
TLDR
The data support the conclusion that REDD1 functions up‐stream of tuberin to down‐regulate the mTOR pathway in response to deferasirox, and may be an antiproliferative agent in some myeloid leukemias, especially patients who need both iron chelation and reduction of leukemia cells. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 33 REFERENCES
The new orally active iron chelator ICL670A exhibits a higher antiproliferative effect in human hepatocyte cultures than O-trensox.
TLDR
It is suggested that ICL670A has the most efficient antitumoral effect, blocks cell proliferation by a pathway different of O-trensox and may constitute a potential drug for anticancer therapy. Expand
Iron mobilization, cytoprotection, and inhibition of cell proliferation in normal and transformed rat hepatocyte cultures by the hydroxypyridinone CP411, compared to CP20: a biological and physicochemical study.
TLDR
CP411 is more efficient to protect the hepatocyte from the toxic effect of iron load and to inhibit tumor cell proliferation since equimolar solutions of the two chelators in an acellular system exhibit the same ability to inhibit the Fenton reaction. Expand
Inhibition of iron toxicity in rat and human hepatocyte cultures by the hydroxypyridin-4-ones CP20 and CP94.
TLDR
The bidentate chelators CP20 and CP94 appeared to be as effective as the hexadentate chelator desferrioxamine (50 microM) in the protection of rat and human hepatocytes against the toxic effect of iron load achieved by culturing the cells for 1 day in the presence of 50 microM iron citrate. Expand
Antiproliferative effect of deferiprone on the Hep G2 cell line.
TLDR
Results show that CP20 as well as deferoxamine inhibit HepG2 cell proliferation and block cell cycle in the S phase, and iron chelation efficiency in the culture model was studied. Expand
Antiproliferative and apoptotic effects of O-Trensox, a new synthetic iron chelator, on differentiated human hepatoma cell lines.
TLDR
The results show that TRX, at concentrations of 20-50 microM, strongly inhibits cell proliferation and induces apoptosis in proliferating and non-proliferating HepG2 and HBG cells, respectively, and DFO is not a strong inducer of apoptosis. Expand
ICL670A: a new synthetic oral chelator: evaluation in hypertransfused rats with selective radioiron probes of hepatocellular and reticuloendothelial iron stores and in iron-loaded rat heart cells in culture.
TLDR
Results indicate that ICL670A given orally is 4 to 5 times more effective than parenteral deferoxamine (DFO) in promoting the excretion of chelatable iron from hepatocellular iron stores. Expand
Iron may induce both DNA synthesis and repair in rat hepatocytes stimulated by EGF/pyruvate.
TLDR
DNA synthesis is increased in the presence of iron in rat hepatocyte cultures stimulated by EGF/pyruvate, and they suggest that DNA synthesis is likely to be related both to cell proliferation and to DNA repair. Expand
Cytotoxic activity of deferiprone, maltol and related hydroxyketones against human tumor cell lines.
TLDR
The present study suggested that the antitumor activity of hydroxyketones may be modified by Fe3+ concentration. Expand
Inhibition of polyamine synthesis induces p53 gene expression but not apoptosis.
TLDR
Investigation of the effect of decreasing cellular polyamines on p53 gene expression and apoptosis in small intestinal epithelial (IEC-6) cells suggests that increased expression of the p53 genes may play an important role in growth inhibition caused by polyamine depletion. Expand
Polyamine modulation of iron uptake in CHO cells.
TLDR
It is demonstrated that the cell polyamine transport system is a potential cell entry pathway for iron, and the studied polyamines, spermine and spermidine, may be components of the pool of transferrin-independent iron-chelating vectors, which have recently attracted the attention of many investigators. Expand
...
1
2
3
4
...