Re: Dying of leukemia - any hope?

From: doe (ironjustice_at_aol.comdoe)
Date: 07/17/04 

Date: 17 Jul 2004 19:25:51 GMT

>Subject: Dying of leukemia - any hope?
>From: "Robert" projecttoday@yahoo.com
>Date: 7/12/2004 4:44 PM Mountain Daylight Time
>Message-id: <10f6571sagc4008@corp.supernews.com>

>Do we have to give up?
>

Yep .. meat . . that .. is ..

<<snip>>
at least 230 times more active in suppressing the growth of L1210 murine
leukemia cells
<<snip>>

J Med Chem. 2003 Dec 4;46(25):5478-83. Related Articles, Links

  
Polyamine-iron chelator conjugate.

Bergeron RJ, McManis JS, Franklin AM, Yao H, Weimar WR.

Department of Medicinal Chemistry, University of Florida, Gainesville, Florida
32610-0485, USA. bergeron@mc.cop.ufl.edu

The current study demonstrates unequivocally that polyamines can serve as
vectors for the intracellular delivery of the bidentate chelator
1,2-dimethyl-3-hydroxypyridin-4-one (L1). The polyamine-hydroxypyridinone
conjugate 1-(12-amino-4,9-diazadodecyl)-2-methyl-3-hydroxy-4(1H)-pyridinone is
assembled from spermine and 3-O-benzylmaltol. The conjugate is shown to form a
3:1 complex with Fe(III) and to be taken up by the polyamine transporter
1900-fold against a concentration gradient. The K(i) of the conjugate is 3.7
microM vs spermidine for the polyamine transporter. The conjugate is also at
least 230 times more active in suppressing the growth of L1210 murine leukemia
cells than is the parent ligand, decreases the activities of the polyamine
biosynthetic enzymes ornithine decarboxylase and S-adenosylmethionine
decarboxylase, and upregulates spermidine-spermine N (1)-acetyltransferase.
However, the effect on native polyamine pools is a moderate one. These findings
are in keeping with the idea that polyamines can also serve as efficient
vectors for the intracellular delivery of other iron chelators.

PMID: 14640556 [PubMed - indexed for MEDLINE]

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Life Sci. 1992;50(26):2059-65. Related Articles, Links

Iron deprivation decreases ribonucleotide reductase activity and DNA synthesis.

Furukawa T, Naitoh Y, Kohno H, Tokunaga R, Taketani S.

Department of Hygiene, Kansai Medical University, Osaka, Japan.

The effects of the iron-chelator, desferrioxamine, and monoclonal antibodies
against transferrin receptors on DNA synthesis and ribonucleotide reductase
activity were examined in human leukemia K562 cells. Treatment of the cells
with desferrioxamine resulted in decreases of ribonucleotide reductase
activity, DNA synthesis, and cell growth. Exposure of the cells to
anti-transferrin receptor antibody, 42/6, which blocks iron supplement into
cells caused decreases of ribonucleotide reductase activity and DNA synthesis,
in a parallel fashion. Decreases of ribonucleotide reductase activity and DNA
synthesis by 42/6 were restored by the addition of ferric nitriloacetate. These
results indicate that ribonucleotide reductase activity is dependent on the
iron-supply and also regulates cell proliferation.

PMID: 1608289 [PubMed - indexed for MEDLINE]

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Tom

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Tom
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Relevant Pages

  • Re: Dying of leukemia - any hope?
    ... So what's a polyamine-iron chelator conjugate? ... > microM vs spermidine for the polyamine transporter. ... > cells than is the parent ligand, decreases the activities of the polyamine ... > Iron deprivation decreases ribonucleotide reductase activity and DNA ...
    (sci.med.diseases.cancer)
  • Re: Dying of leukemia - any hope?
    ... >> microM vs spermidine for the polyamine transporter. ... >> cells than is the parent ligand, decreases the activities of the polyamine ... >> Iron deprivation decreases ribonucleotide reductase activity and DNA ...
    (sci.med.diseases.cancer)
  • Re: Dying of leukemia - any hope?
    ... >>>> Iron deprivation decreases ribonucleotide reductase activity and DNA ... >>>> activity were examined in human leukemia K562 cells. ... >>>> activity, DNA synthesis, and cell growth. ...
    (sci.med.diseases.cancer)