Iron chelators / cancer
ironjustice_at_aol.com
Date: 02/24/05
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Date: 24 Feb 2005 05:56:30 -0800
Curr Top Med Chem. 2004;4(15):1623-35. Related Articles, Links
Iron chelators in cancer chemotherapy.
Buss JL, Greene BT, Turner J, Torti FM, Torti SV.
Department of Biochemistry, Wake Forest University Health Sciences,
Medical Center Blvd., Winston-Salem, NC 27157, USA.
Iron chelators may be of value as therapeutic agents in the treatment
of cancer. They may act by depleting iron, a necessary nutrient, and
limiting tumor growth. Alternatively or additionally, they may form
redox-active metal complexes that cause oxidative stress via production
of reactive oxygen species, damaging critical intracellular targets and
thereby eliciting a cytotoxic response. Studies in vitro have evaluated
the structure-activity relationships and mechanism of action of many
classes of iron chelators, including desferrioxamine (DFO), pyridoxal
isonicotinoyl hydrazone (PIH) analogs, desferrithiocin (DFT) analogs,
tachpyridine, the heterocyclic carboxaldehyde thiosemicarbazones, and
O-Trensox. Animal studies have confirmed the antitumor activity of
several chelators. Dexrazoxane has been approved for use in combination
with doxorubicin, and its effectiveness in allowing higher doses of
doxorubicin to be administered is, in part, based on the interactions
of both drugs with iron. Clinical trials of the antitumor activity of
chelators have been largely limited to DFO, which has been extensively
studied as a consequence of its approved use for treatment of secondary
iron overload. While the modest antitumor effects of DFO are
encouraging, it is likely that more effective iron chelators may be
identified.
Publication Types:
Review
Review, Tutorial
PMID: 15579100 [PubMed - indexed for MEDLINE]
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