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Blood. 2004 May 18 [Epub ahead of print] Related
Articles, Links
Novel Di-2-Pyridyl-Derived Iron Chelators with Marked and
Selective Anti-Tumor Activity: In Vitro and In Vivo
Assessment.
Yuan J, Lovejoy DB, Richardson DR.
Children's Cancer Institute Australia, University of New
South Wales, Sydney, NSW, Australia.
Aroylhydrazone and thiosemicarbazone iron (Fe) chelators
possess potent anti-tumor activity (Lovejoy DB, Richardson
DR Blood 2002;100:666-676). The current aim was to examine
the anti-tumor effects and mechanisms of action of a novel
series of Fe chelators, the di-2-pyridyl thiosemicarbazones.
Of seven new chelators synthesized, four showed pronounced
anti-proliferative effects. The most active chelator was
Dp44mT, which had marked and selective anti-tumor activity
eg., IC50 of 0.03 micro M in neuroepithelioma cells compared
to >25 micro M in mortal fibroblasts. Indeed, this anti-
proliferative activity was the greatest yet observed for an
Fe chelator, having greater efficacy than the cytotoxic
ligand, 311, and being comparable to the anti-tumor agent,
doxorubicin. Strikingly, Dp44mT significantly (p < 0.01)
decreased tumor weight in mice to 47% of the control after
only 5 days, while there was no marked change in animal
weight or hematological indices. TUNEL staining demonstrated
apoptosis in tumors taken from mice treated with Dp44mT, and
this chelator caused a marked increase of caspase-3 activity
in M109 cells. Caspase activation was at least partially
mediated by the release of mitochondrial holo-cytochrome c
(h-cytc) after incubation with Dp44mT. In conclusion, Dp44mT
is a novel highly effective anti-tumor agent in vitro and in
vivo that induces apoptosis.
PMID: 15150082 [PubMed - as supplied by publisher]
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Who loves ya. Tom Jesus Was A Vegetarian!
http://jesuswasavegetarian.7h.com Man Is A Herbivore!
http://pages.ivillage.com/ironjustice/manisaherbivore DEAD
PEOPLE WALKING
http://pages.ivillage.com/ironjustice/deadpeoplewalking
Articles, Links
Novel Di-2-Pyridyl-Derived Iron Chelators with Marked and
Selective Anti-Tumor Activity: In Vitro and In Vivo
Assessment.
Yuan J, Lovejoy DB, Richardson DR.
Children's Cancer Institute Australia, University of New
South Wales, Sydney, NSW, Australia.
Aroylhydrazone and thiosemicarbazone iron (Fe) chelators
possess potent anti-tumor activity (Lovejoy DB, Richardson
DR Blood 2002;100:666-676). The current aim was to examine
the anti-tumor effects and mechanisms of action of a novel
series of Fe chelators, the di-2-pyridyl thiosemicarbazones.
Of seven new chelators synthesized, four showed pronounced
anti-proliferative effects. The most active chelator was
Dp44mT, which had marked and selective anti-tumor activity
eg., IC50 of 0.03 micro M in neuroepithelioma cells compared
to >25 micro M in mortal fibroblasts. Indeed, this anti-
proliferative activity was the greatest yet observed for an
Fe chelator, having greater efficacy than the cytotoxic
ligand, 311, and being comparable to the anti-tumor agent,
doxorubicin. Strikingly, Dp44mT significantly (p < 0.01)
decreased tumor weight in mice to 47% of the control after
only 5 days, while there was no marked change in animal
weight or hematological indices. TUNEL staining demonstrated
apoptosis in tumors taken from mice treated with Dp44mT, and
this chelator caused a marked increase of caspase-3 activity
in M109 cells. Caspase activation was at least partially
mediated by the release of mitochondrial holo-cytochrome c
(h-cytc) after incubation with Dp44mT. In conclusion, Dp44mT
is a novel highly effective anti-tumor agent in vitro and in
vivo that induces apoptosis.
PMID: 15150082 [PubMed - as supplied by publisher]
------------------------------------------------------------
--------------
------
Who loves ya. Tom Jesus Was A Vegetarian!
http://jesuswasavegetarian.7h.com Man Is A Herbivore!
http://pages.ivillage.com/ironjustice/manisaherbivore DEAD
PEOPLE WALKING
http://pages.ivillage.com/ironjustice/deadpeoplewalking