ironjustice
2012-10-18 20:54:00 UTC
The Iron Chelator, Deferasirox, as a Novel Strategy for Cancer
Treatment: Oral Activity Against Human Lung Tumor Xenografts and
Molecular Mechanism of Action.
Lui GY, Obeidy P, Ford SJ, Tselepis C, Sharp DM, Jansson PJ,
Kalinowski DS, Kovacevic Z, Lovejoy DB, Richardson DR.
Mol Pharmacol. 2012 Oct 16.
The University of Sydney;
Abstract
Deferasirox is an orally-effective iron chelator currently used for
the treatment of iron (Fe) overload disease and has been implemented
as an alternative to the "gold standard" chelator, desferrioxamine
(DFO).
Earlier studies demonstrated that DFO has anti-cancer activity due to
its ability to deplete cancer cells of Fe.
In this investigation, we examined the in vitro and in vivo activity
of deferasirox against cells from human solid tumors.
To date, there have been no studies to investigate the effect of
deferasirox on these types of tumors in vivo.
Deferasirox demonstrated similar activity at inhibiting proliferation
of DMS-53 lung carcinoma and SK-N-MC neuroepithelioma cell lines when
compared to DFO.
Further, deferasirox was generally similar or slightly more effective
than DFO at mobilizing cellular (59)Fe and inhibiting iron uptake from
Tf depending on the cell-type.
However, deferasirox potently inhibited DMS-53 xenograft growth in
nude mice when given by oral gavage, with no marked alterations in
normal tissue histology.
To understand the anti-tumor activity of deferasirox, we investigated
its effect on the expression of molecules that play key roles in
metastasis, cell cycle control and apoptosis.
We demonstrated that deferasirox increased expression of the
metastasis suppressor protein, N-myc downstream regulated gene-1
(NDRG1), and up-regulated the cyclin-dependent kinase inhibitor
p21(CIP1/WAF1), while decreasing cyclin D1 levels.
Moreover, this agent increased the expression of apoptosis markers,
including cleaved caspase-3 and cleaved poly [ADP-ribose] polymerase
1.
Collectively, we demonstrate that deferasirox is an orally-effective
anti-tumor agent against solid tumors.
PMID:23074173
Who loves ya.
Tom
Jesus Was A Vegetarian!
http://tinyurl.com/2r2nkh
Man Is A Herbivore!
http://tinyurl.com/4rq595
DEAD PEOPLE WALKING
http://tinyurl.com/zk9fk
Treatment: Oral Activity Against Human Lung Tumor Xenografts and
Molecular Mechanism of Action.
Lui GY, Obeidy P, Ford SJ, Tselepis C, Sharp DM, Jansson PJ,
Kalinowski DS, Kovacevic Z, Lovejoy DB, Richardson DR.
Mol Pharmacol. 2012 Oct 16.
The University of Sydney;
Abstract
Deferasirox is an orally-effective iron chelator currently used for
the treatment of iron (Fe) overload disease and has been implemented
as an alternative to the "gold standard" chelator, desferrioxamine
(DFO).
Earlier studies demonstrated that DFO has anti-cancer activity due to
its ability to deplete cancer cells of Fe.
In this investigation, we examined the in vitro and in vivo activity
of deferasirox against cells from human solid tumors.
To date, there have been no studies to investigate the effect of
deferasirox on these types of tumors in vivo.
Deferasirox demonstrated similar activity at inhibiting proliferation
of DMS-53 lung carcinoma and SK-N-MC neuroepithelioma cell lines when
compared to DFO.
Further, deferasirox was generally similar or slightly more effective
than DFO at mobilizing cellular (59)Fe and inhibiting iron uptake from
Tf depending on the cell-type.
However, deferasirox potently inhibited DMS-53 xenograft growth in
nude mice when given by oral gavage, with no marked alterations in
normal tissue histology.
To understand the anti-tumor activity of deferasirox, we investigated
its effect on the expression of molecules that play key roles in
metastasis, cell cycle control and apoptosis.
We demonstrated that deferasirox increased expression of the
metastasis suppressor protein, N-myc downstream regulated gene-1
(NDRG1), and up-regulated the cyclin-dependent kinase inhibitor
p21(CIP1/WAF1), while decreasing cyclin D1 levels.
Moreover, this agent increased the expression of apoptosis markers,
including cleaved caspase-3 and cleaved poly [ADP-ribose] polymerase
1.
Collectively, we demonstrate that deferasirox is an orally-effective
anti-tumor agent against solid tumors.
PMID:23074173
Who loves ya.
Tom
Jesus Was A Vegetarian!
http://tinyurl.com/2r2nkh
Man Is A Herbivore!
http://tinyurl.com/4rq595
DEAD PEOPLE WALKING
http://tinyurl.com/zk9fk