Iron Chelation For Breast Cancer

Desferal inhibits breast tumor growth and does not interfere with the
tumoricidal activity of doxorubicin
HOKE Eileen M. ; MAYLOCK Caroline A. ; SHACTER Emily ;

Abstract
Desferal is a clinically approved iron chelator used to treat iron
overload.
Doxorubicin is an anthracycline cancer chemotherapy drug used in the
treatment of breast cancer.
It can undergo redox cycling in the presence ofiron to produce
reactive oxygen species.
The oxidant-generating activity of doxorubicin is thought to be
responsible for the cardiotoxic side effects of the drug, but it is
unclear whether it is also required for its anti-tumor activity.
To test whether an iron-chelating antioxidant would interfere with the
tumor-killing activity of doxorubicin, nude mice were transplanted
with xenografts of human breast cancer MDA-MB 231 cells and then
treated with doxorubicin and/or desferal.
Not only did desferal not interfere with the anti-tumor activity of
doxorubicin, it inhibited tumor growth on its own.
In vitro studies confirmed that desferal inhibits breast tumor
growth.
However, it did not induce apoptosis, nor did it induce cell cycle
arrest.
Instead, desferal caused cytostasis, apparently through iron
depletion.
The cytostatic activity of desferal was partially ameliorated by
pretreatment with iron-saturated transferrin, and transferrin receptor
expression on breast cancer cells nearly doubled after exposure to
desferal.
In contrast to its effect on tumor cells, desferal did not inhibit
growth of normal breast epithelial cells.
The data indicate that the anti-tumor activity of doxorubicin is not
dependent on iron-mediated ROS production.
Furthermore, desferal may have utility as an adjunctive chemotherapy
due to its ability to inhibit breast tumor growth and cardiotoxic side
effects without compromising the tumor-killing activity of an
anthracycline chemotherapy drug.
Revue / Journal Title
Free radical biology & medicine ISSN 0891-5849 CODEN FRBMEH
Source / Source
2005, vol. 39, no3, pp. 403-411 [9 page(s) (article)]
Langue / Language
Anglais

Editeur / Publisher
Elsevier Science, New York, NY, ETATS-UNIS (1987) (Revue)

Mots-clés d'auteur / Author Keywords
Free radicals ; Breast cancer ; Chemotherapy ; Doxorubicin ;
Desferal ; Iron ; Oxidants ; Antioxidants ;
Localisation / Location
INIST-CNRS, Cote INIST : 20995, 35400013236444.0110


Copyright 2007 INIST-CNRS. All rights reserved


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DEAD PEOPLE WALKING
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On Aug 29, 1:30*pm, ironjustice <teamtan...@hotmail.com> wrote: iron
and cancer<<

http://www.cancerproject.org/protect...ength/iron.php

Building Your Strength Against Cancer - Iron: The Double-Edged Sword
Iron encourages the formation of cancer-causing free radicals. Of
course, the body needs a certain amount of iron for healthy blood
cells. But beyond this rather small amount, iron becomes a dangerous
substance, acting as a catalyst for the formation of free radicals.
Because of this, research studies have shown that higher amounts of
iron in the blood mean higher cancer risk.23

Once iron is absorbed by the digestive tract, the body stores it. Most
of us accumulate much more iron than we need. In spite of the
advertising from iron supplement manufacturers, "iron overload" is
much more common in America than iron deficiency. The reason is the
daily diet of red meats, which contributes much more iron than most
people can safely handle over the long run. A diet of grains,
vegetables, fruits, and beans provides adequate iron, without the risk
of overload.

It is easy to check whether your body has accumulated too much stored
iron. The following set of tests will check for both iron deficiency
and iron overload. The more general hemoglobin and hematocrit tests
are not sufficient. Although general guidelines are given here, the
tests should be interpreted by your doctor:

Serum ferritin (normal values are 12-200 mcg/l of serum)
Serum iron
Total iron binding capacity (TIBC)
Doctors divide the serum-iron value by the TIBC. The result should be
16 to 50 percent for women and 16 to 62 percent for men. Results above
these norms indicate excess iron. Results below these norms indicate
iron deficiency. A further test sometimes used to check for iron
deficiency is the red cell protoporphyrin test. A result greater than
70 units is considered abnormal. If two of these three values (serum
ferritin, serum iron/TIBC, and red cell protoporphyrin) are normal,
iron-deficiency anemia is not likely. Serum iron and TIBC should be
measured after fasting overnight.

Unfortunately, the body has no way to rid itself of excess iron.
Believe it or not, the only way to predictably reduce excessive iron
stores is by donating blood. So this altruistic act can have health
benefits for the donor as well.


Who loves ya.
Tom


Jesus Was A Vegetarian!
http://tinyurl.com/634q5a


Man Is A Herbivore!
http://tinyurl.com/4rq595


DEAD PEOPLE WALKING
http://tinyurl.com/zk9fk





> Desferal inhibits breast tumor growth and does not interfere with the
> tumoricidal activity of doxorubicin
> HOKE Eileen M. ; MAYLOCK Caroline A. ; SHACTER Emily ;
>
> Abstract
> Desferal is a clinically approved iron chelator used to treat iron
> overload.
> Doxorubicin is an anthracycline cancer chemotherapy drug used in the
> treatment of breast cancer.
> It can undergo redox cycling in the presence ofiron to produce
> reactive oxygen species.
> The oxidant-generating activity of doxorubicin is thought to be
> responsible for the cardiotoxic side effects of the drug, but it is
> unclear whether it is also required for its anti-tumor activity.
> To test whether an iron-chelating antioxidant would interfere with the
> tumor-killing activity of doxorubicin, nude mice were transplanted
> with xenografts of human breast cancer MDA-MB 231 cells and then
> treated with doxorubicin and/or desferal.
> Not only did desferal not interfere with the anti-tumor activity of
> doxorubicin, it inhibited tumor growth on its own.
> In vitro studies confirmed that desferal inhibits breast tumor
> growth.
> However, it did not induce apoptosis, nor did it induce cell cycle
> arrest.
> Instead, desferal caused cytostasis, apparently through iron
> depletion.
> The cytostatic activity of desferal was partially ameliorated by
> pretreatment with iron-saturated transferrin, and transferrin receptor
> expression on breast cancer cells nearly doubled after exposure to
> desferal.
> In contrast to its effect on tumor cells, desferal did not inhibit
> growth of normal breast epithelial cells.
> The data indicate that the anti-tumor activity of doxorubicin is not
> dependent on iron-mediated ROS production.
> Furthermore, desferal may have utility as an adjunctive chemotherapy
> due to its ability to inhibit breast tumor growth and cardiotoxic side
> effects without compromising the tumor-killing activity of an
> anthracycline chemotherapy drug.
> Revue / Journal Title
> Free radical biology & medicine * ISSN 0891-5849 * CODEN FRBMEH
> Source / Source
> 2005, vol. 39, no3, pp. 403-411 [9 page(s) (article)]
> Langue / Language
> Anglais
>
> Editeur / Publisher
> Elsevier Science, New York, NY, ETATS-UNIS (1987) (Revue)
>
> Mots-clés d'auteur / Author Keywords
> Free radicals ; Breast cancer ; Chemotherapy ; Doxorubicin ;
> Desferal ; Iron ; Oxidants ; Antioxidants ;
> Localisation / Location
> INIST-CNRS, Cote INIST : 20995, 35400013236444.0110
>
> Copyright 2007 INIST-CNRS. All rights reserved
>
> Who loves ya.
> Tom
>
> Jesus Was A Vegetarian!http://tinyurl.com/634q5a
>
> Man Is A Herbivore!http://tinyurl.com/4rq595
>
> DEAD PEOPLE WALKINGhttp://tinyurl.com/zk9fk

> Iron encourages the formation of cancer-causing free radicals. Of
> course, the body needs a certain amount of iron for healthy blood
> cells. But beyond this rather small amount, iron becomes a dangerous
> substance, acting as a catalyst for the formation of free radicals.
> Because of this, research studies have shown that higher amounts of
> iron in the blood mean higher cancer risk.

TCDD, a dioxin, is the most potent activator of the AhR-mediated
cellular detox exzymes (CYP1A1, CYP1A2, CYP1B1) all of which require
iron. TCDD hyperactivates cellular response to substrates such as
pollutants, pesticides, herbicide, fungicides, endo/exogenous
estrogens, etc. Genetic variations make some more sensative than
others. Most people have accumulated their current TCDD levels via
dietary animal fats during the past decades, before studies began to
expose it's toxicity and long half life of 10 year in humans.
Currently, there are no effective methods of removing TCDD from body.
Currently, World Health Oganization has set the daily tolerable limit
to 2.3 pg/kg which translate to 163 pico grams for a 70 kg person. A
pico is 1 / 1,000,000,000,000 th.


TCDD modulates the induction of DNA strand breaks and poly(ADP-ribose)
polymerase-1 activation by 17beta-estradiol in human breast carcinoma
cells through alteration of CYP1A1 and CYP1B1 expression.

The primary purpose of this research is to investigate the effects of
2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD) pretreatment and estrogen
receptors-alpha (ER alpha) status on the induction of DNA damage by
17beta-estradiol (E 2) in human ER alpha(+)/MCF-7 and ER alpha(-)/MDA-
MB-231 breast cancer cells. Results indicated that E 2 (0.1-100 nM)
alone induced significant increases in cytotoxic response, reactive
oxygen species (ROS) generation, and glutathione depletion in MDA-
MB-231 cells but not in MCF-7 cells. At noncytotoxic concentrations, E
2 induced dose-related reduction in intracellular NAD(P)H in MDA-
MB-231 cells through decreases in intracellular NAD (+) mediated by
poly(ADP-ribose) polymerase-1 (PARP-1) activation as determined by
detection of the presence of polymers of ADP-ribose-modified PARP-1
using Western blotting. Further investigation using the single-cell
gel electrophoresis (Comet) assay confirmed that the PARP-1 activation
induced by estrogen in MDA-MB-231 was due to increases in the number
of DNA strand breaks. This evidence indicates that E 2 induces
decreases in intracellular NAD(P)H and NAD (+) in MDA-MB-231 cells
through PARP-1 activation mediated by the formation of DNA strand
breaks. Further investigation indicated that the cytotoxic and DNA-
damaging effects induced by E 2 in MDA-MB-231 cells were completely
blocked by pretreatment of TCDD (10 nM for 72 h). In contrast, with
TCDD pretreatment, significant increases in cytotoxic response, ROS
generation, glutathione (GSH) depletion, DNA strand breaks, and PARP-1
activation were detected in MCF-7 cells exposed to E 2. We
demonstrated that TCDD modulated the differential induction of DNA
damage by estrogen in MDA-MB-231 and MCF-7 cells primarily through the
inducibility of cytochrome P450 1A1 and 1B1 expression. Overall, this
evidence suggests that TCDD is capable of inducing imbalances in the
expression of enzymes responsible for the bioactivation of estrogen
leading to the subsequent accumulation of DNA damage and initiation of
DNA repair in MDA-MB-231 and MCF-7 cells. Furthermore, we confirmed
that ER alpha plays a protective role in modulating the induction of
DNA damage by E 2 in human breast cancer cells. PMID: 18558727


For more similar abstracts, search www.pubmed.com for "dioxin breast
cancer".

On Aug 29, 2:07*pm, jay <jaym1...@hotmail.com> wrote: iron
and cancer<<

http://www.cancerproject.org/protect...ength/iron.php


Building Your Strength Against Cancer - Iron: The Double-Edged Sword
Iron encourages the formation of cancer-causing free radicals. Of
course, the body needs a certain amount of iron for healthy blood
cells. But beyond this rather small amount, iron becomes a dangerous
substance, acting as a catalyst for the formation of free radicals.
Because of this, research studies have shown that higher amounts of
iron in the blood mean higher cancer risk.23


Once iron is absorbed by the digestive tract, the body stores it.
Most
of us accumulate much more iron than we need. In spite of the
advertising from iron supplement manufacturers, "iron overload" is
much more common in America than iron deficiency. The reason is the
daily diet of red meats, which contributes much more iron than most
people can safely handle over the long run. A diet of grains,
vegetables, fruits, and beans provides adequate iron, without the
risk
of overload.


It is easy to check whether your body has accumulated too much stored
iron. The following set of tests will check for both iron deficiency
and iron overload. The more general hemoglobin and hematocrit tests
are not sufficient. Although general guidelines are given here, the
tests should be interpreted by your doctor:


Serum ferritin (normal values are 12-200 mcg/l of serum)
Serum iron
Total iron binding capacity (TIBC)
Doctors divide the serum-iron value by the TIBC. The result should be
16 to 50 percent for women and 16 to 62 percent for men. Results
above
these norms indicate excess iron. Results below these norms indicate
iron deficiency. A further test sometimes used to check for iron
deficiency is the red cell protoporphyrin test. A result greater than
70 units is considered abnormal. If two of these three values (serum
ferritin, serum iron/TIBC, and red cell protoporphyrin) are normal,
iron-deficiency anemia is not likely. Serum iron and TIBC should be
measured after fasting overnight.


Unfortunately, the body has no way to rid itself of excess iron.
Believe it or not, the only way to predictably reduce excessive iron
stores is by donating blood. So this altruistic act can have health
benefits for the donor as well.


Who loves ya.
Tom


Jesus Was A Vegetarian!
http://tinyurl.com/634q5a


Man Is A Herbivore!
http://tinyurl.com/4rq595


DEAD PEOPLE WALKING
http://tinyurl.com/zk9fk

On Aug 29, 2:33*pm, ironjustice <teamtan...@hotmail.com> wrote: cancer
<<

http://gut.bmj.com/cgi/content/extract/55/10/1384

Epidemiological data strongly support a role for dietary and haem iron
in colorectal carcinogenesis through multiple pathways
--------------------------------------------------------------------------------

"Dietary iron may be involved in the development of colorectal
adenomas (and particularly proximal adenomas).3 Dietary haem iron
(through its effect on epithelial proliferation) is associated with an
increased risk of proximal colon cancer, especially in women"


Who loves ya.
Tom


Jesus Was A Vegetarian!
http://tinyurl.com/634q5a


Man Is A Herbivore!
http://tinyurl.com/4rq595


DEAD PEOPLE WALKING
http://tinyurl.com/zk9fk

On Aug 29, 2:44*pm, ironjustice <teamtan...@hotmail.com> wrote: cancer
<<


COLORECTAL CANCER

Modulation of iron transport proteins in human colorectal
carcinogenesis
M J Brookes1, S Hughes1, F E Turner2, G Reynolds1, N Sharma1, T
Ismail1, G Berx3, A T McKie4, N Hotchin2, G J Anderson5, T Iqbal6,*, C
Tselepis1,*
1 Cancer Research UK Institute for Cancer Studies, University of
Birmingham, UK
2 School of Biosciences, University of Birmingham, UK
3 Department for Molecular Biomedical Research, VIB-Ghent University,
Belgium
4 Division of Nutritional Sciences, Kings College London, UK
5 Iron Metabolism Laboratory, Queensland Institute of Medical
Research, PO Royal Brisbane Hospital, Brisbane, Queensland, Australia
6 Gastroenterology Unit, Walsgrave Hospital, UK


Correspondence to:
Correspondence to:
Dr C Tselepis
Cancer Research UK Institute for Cancer Studies, University of
Birmingham, Vincent Drive, Birmingham B15 2TH, UK;
c.tselepis@bham.ac.uk



ABSTRACT
Background and aims: Total body iron and high dietary iron intake are
risk factors for colorectal cancer. To date there is no comprehensive
characterisation of iron transport proteins in progression to
colorectal carcinoma. In this study, we examined expression of iron
import (duodenal cytochrome b (DCYTB), divalent metal transporter 1
(DMT1), and transferrin receptor 1 (TfR1)) and export (hephaestin
(HEPH) and ferroportin (FPN)) proteins in colorectal carcinoma.

Methods: Perl’s staining was used to examine colonocyte iron content.
Real time polymerase chain reaction (PCR) and western blotting were
used to examine mRNA and protein levels of the molecules of interest
in 11 human colorectal cancers. Semiquantitative immunohistochemistry
was used to verify protein levels and information on cellular
localisation. The effect of iron loading on E-cadherin expression in
SW480 and Caco-2 cell lines was examined by promoter assays, real time
PCR and western blotting.

Results: Perl’s staining showed increased iron in colorectal cancers,
and there was a corresponding overexpression of components of the
intracellular iron import machinery (DCYTB, DMT1, and TfR1). The iron
exporter FPN was also overexpressed, but its intracellular location,
combined with reduced HEPH levels, suggests reduced iron efflux in the
majority of colorectal cancers examined. Loss of HEPH and FPN
expression was associated with more advanced disease. Iron loading
Caco-2 and SW480 cells caused cellular proliferation and E-cadherin
repression.

Conclusions: Progression to colorectal cancer is associated with
increased expression in iron import proteins and a block in iron
export due to decreased expression and aberrant localisation of HEPH
and FPN, respectively. This results in increased intracellular iron
which may induce proliferation and repress cell adhesion.



--------------------------------------------------------------------------------

Abbreviations: CRC, colorectal cancer; DCYTB, duodenal cytochrome b;
DMT1, divalent metal transporter 1; TfR1, transferrin receptor 1;
HEPH, hephaestin; FPN, ferroportin; PCR, polymerase chain reaction;
CK, cytokeratin; PBS, phosphate buffered saline; DAB
diaminobenzidine, ; LGD, low grade dysplastic adenomas, HGD, high
grade dysplastic adenomas


Keywords: E-cadherin; iron; colon; cancer


Who loves ya.
Tom


Jesus Was A Vegetarian!
http://tinyurl.com/634q5a


Man Is A Herbivore!
http://tinyurl.com/4rq595


DEAD PEOPLE WALKING
http://tinyurl.com/zk9fk