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Home > Archive > Pathology > March 2006 > Cellular iron / cancer cell proliferation / vitamin C
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Cellular iron / cancer cell proliferation / vitamin C
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| ironjustice@aol.com 2006-03-03, 10:58 am |
| Effects of transferrin receptor blockade on cancer cell proliferation
and hypoxia-inducible factor function and their differential regulation
by ascorbate.
Jones DT, Trowbridge IS, Harris AL
Cancer Res. 2006 Mar 1; 66(5): 2749-56
Cellular iron is needed for cell survival and hydroxylation of
hypoxia-inducible factor-1alpha (HIF-alpha) by prolyl hydroxylases
(PHD). One mechanism of iron uptake is mediated by the cell surface
transferrin receptor (TfR). Because iron is required for cell growth
and suppression of HIF-alpha levels, we tested the effects of the two
anti-TfR monoclonal antibodies (mAb) E2.3 and A27.15 on growth of
breast cancer cells and induction of HIF-alpha and hypoxia-regulated
genes. Treatment with both mAbs together synergistically inhibited cell
proliferation in a dose-responsive manner by up to 80% following 8 days
of exposure, up-regulated HIF-1alpha and HIF transcription targets,
down-regulated TfR expression, and down-regulated cellular labile iron
pool by 60%. Because combined treatment with anti-TfR mAbs resulted in
the up-regulation of the hypoxia pathway, which may increase tumor
angiogenesis, we analyzed the effects of ascorbate on cell viability
and HIF-1alpha levels in cells treated with both anti-TfR mAbs
together, as ascorbate has been shown to be required by PHD enzymes for
full catalytic activity. Ascorbate at physiologic concentrations (25
mumol/L) suppressed HIF-1alpha protein levels and HIF transcriptional
targets in anti-TfR mAb-treated cells but did not suppress the
antiproliferative effect of the mAbs. These results indicate that the
addition of ascorbate increased the activity of the PHD enzymes in
down-regulating HIF but not the proliferation of iron-starved anti-TfR
mAb-treated cells. The use of anti-TfR mAbs and ascorbate in inhibiting
both cell proliferation and HIF-1alpha and angiogenesis under normoxic
conditions may be of therapeutic use. (Cancer Res 2006; 66(5):
2749-56).
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Tom
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"ironjustice@aol.com" wrote:
> Effects of transferrin receptor blockade on cancer cell proliferation
> and hypoxia-inducible factor function and their differential regulation
> by ascorbate.
http://en.wikipedia.org/wiki/Vitamin_C
Vitamin C is a water-soluble nutrient essential for life, used by the human
body for many purposes. It is one of a number of such key nutrients called
vitamins.
To the best of scientific knowledge, all animals and plants synthesize
their own vitamin C, except for humans and a small number of other animals,
including, apes, guinea pigs, the red-vented bulbul, a fruit-eating bat and
a species of trout. This has led a minority of scientists, most notably
Linus Pauling to conclude that failure to produce the chemical by an animal
species is a genetic defect and to hypothesize that if it were replaced in
humans to the level found in animals better health would result.
Vitamin C was first isolated in 1928, and in 1932 it was proved to be the
agent which prevents scurvy. In 1937 Albert Szent-Györgyi was awarded the
Nobel Prize for this feat.
Vitamin C is a weak acid, called ascorbic acid or ascorbate (an
L-enantiomer of ascorbic acid; an L-enantiomer is simply one of two mirror
image forms of the same chemical molecular structure, see optical isomers).
The active part of the substance is the ascorbate ion, which can express
itself as either an acid or a salt of ascorbate that is neutral or slightly
basic. Commercial vitamin C is often a mix of ascorbic acid, sodium
ascorbate and/or other ascorbates. Some supplements contain in part the
D-enantiomer, which is useless but harmless. See the ascorbic acid article
for a full description of the molecule's chemical properties.
> Jones DT, Trowbridge IS, Harris AL Cancer Res. 2006 Mar 1; 66(5): 2749-56
>
> [...] The use of anti-TfR mAbs and ascorbate in inhibiting
> both cell proliferation and HIF-1alpha and angiogenesis under normoxic
> conditions may be of therapeutic use. (Cancer Res 2006; 66(5): 2749-56).
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