Iron Deprivation In Hepatocellular Carcinoma

[ironjustice]

"Iron chelator"
"Suppresses human HCC tumor growth"

Iron deprivation suppresses hepatocellular carcinoma growth in
experimental studies.
Clin Cancer Res. 2011 Nov 3.
Ba Q, Hao M, Huang H, Hou J, Ge S, Zhang Z, Yin J, Chu R, Jiang LH,
Wang F, Chen K, Liu H, Wang H.
Institute for Nutritional Sciences, Shanghai Institute of Biological
Sciences, Chinese Academy of Sciences.

Abstract
PURPOSE: Hepatocellular carcinoma (HCC) is the third most common cause
of cancer-related death and iron overload is a significant risk factor
in the development of HCC. In this study we investigated the potential
application of depriving iron by a novel iron chelator,
thiosemicarbazone-24 (TSC24), in HCC treatment.

EXPERIMENTAL DESIGN: Two HCC cell lines and HFE knockout (HFE-/-) mice
were used to determine iron chelation efficiency of TSC24. The
anticancer effects of TSC24 on HCC were analyzed in vitro and in
athymic xenograft mouse models.

RESULTS: Treatment with TSC24 significantly decreased the cellular
iron concentration in hepatoma cells and the serum iron concentration
in HFE-/- mice, by blocking iron uptake and interfering with normal
regulation of iron levels. Moreover, the viability of HCC cell lines
was reduced by TSC24. Confirming the mechanism of the agent, this
decrease in viability could be partially rescued by addition of
exogenous iron. TSC24 also suppressed tumor growth in athymic mice
bearing human HCC xenografts in a concentration dependent manner
without apparent toxicity in parallel with a decrease in the serum
iron level. Further studies revealed that TSC24 efficiently triggered
cell cycle arrest and apoptosis in Hep3B and HepG2 cell lines.

CONCLUSIONS: TSC24 is a potent iron chelator that suppresses human HCC
tumor growth by disrupting iron homeostasis, reducing available iron
and triggering cell cycle arrest and apoptosis, without apparent host
toxicity at effective doses. Thus, TSC24 shows great potential for the
treatment of HCC.

PMID:22052937


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[John H. Gohde]

Post by ironjustice
"Iron chelator"
"Suppresses human HCC tumor growth"
Iron deprivation suppresses hepatocellular carcinoma growth in
experimental studies.
Clin Cancer Res. 2011 Nov 3.
Ba Q, Hao M, Huang H, Hou J, Ge S, Zhang Z, Yin J, Chu R, Jiang LH,
Wang F, Chen K, Liu H, Wang H.
Institute for Nutritional Sciences, Shanghai Institute of Biological
Sciences, Chinese Academy of Sciences.
Abstract
PURPOSE: Hepatocellular carcinoma (HCC) is the third most common cause
of cancer-related death and iron overload is a significant risk factor
in the development of HCC. In this study we investigated the potential
application of depriving iron by a novel iron chelator,
thiosemicarbazone-24 (TSC24), in HCC treatment.
EXPERIMENTAL DESIGN: Two HCC cell lines and HFE knockout (HFE-/-) mice
were used to determine iron chelation efficiency of TSC24. The
anticancer effects of TSC24 on HCC were analyzed in vitro and in
athymic xenograft mouse models.
RESULTS: Treatment with TSC24 significantly decreased the cellular
iron concentration in hepatoma cells and the serum iron concentration
in HFE-/- mice, by blocking iron uptake and interfering with normal
regulation of iron levels. Moreover, the viability of HCC cell lines
was reduced by TSC24. Confirming the mechanism of the agent, this
decrease in viability could be partially rescued by addition of
exogenous iron. TSC24 also suppressed tumor growth in athymic mice
bearing human HCC xenografts in a concentration dependent manner
without apparent toxicity in parallel with a decrease in the serum
iron level. Further studies revealed that TSC24 efficiently triggered
cell cycle arrest and apoptosis in Hep3B and HepG2 cell lines.
CONCLUSIONS: TSC24 is a potent iron chelator that suppresses human HCC
tumor growth by disrupting iron homeostasis, reducing available iron
and triggering cell cycle arrest and apoptosis, without apparent host
toxicity at effective doses. Thus, TSC24 shows great potential for the
treatment of HCC.
PMID:22052937
Who loves ya.
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This is NOT original content.

It duplicates what is available at:
http://www.ncbi.nlm.nih.gov/pubmed/22052937

Please STOP polluting these newsgroups with your SPAM or the boogie
bear and Google will get you where you slept, as noted elsewhere on
these newsgroups.

[ironjustice]

On Nov 15, 7:09 am, ironjustice <***@rock.com> wrote:
"Iron chelator" "Suppresses human HCC tumor growth" <<

Iron, hemochromatosis, and hepatocellular carcinoma.
Kowdley KV.
Gastroenterology. 2004 Nov;127(5 Suppl 1):S79-86.
University of Washington, Box 356174, 1959 NE Pacific Street, Seattle,
Washington 98195, USA. ***@u.washington.edu

Abstract
Hereditary hemochromatosis (HH) is associated with an increased risk
for hepatocellular carcinoma (HCC).
The risk previously had been estimated to be as high as 200-fold
increased.
Recent studies suggest that the risk for HCC in HFE -associated HH may
be much lower and occurs predominantly in patients with cirrhosis at
the time of diagnosis.
The risk for HCC also is increased among patients with African iron
overload and possibly in other iron-loading disorders such as
homozygous beta thalassemia.
The greatly increased iron stores in the liver observed in these
disorders can stimulate carcinogenesis via both direct and indirect
pathways.
The prevalence of HCC also appears to be higher among patients with
end-stage liver disease undergoing liver transplantation.
It is not clear whether mildly to moderately increased hepatic iron
stores or HFE mutations are associated independently with an increased
risk for HCC among patients with other types of liver disease.
In this article, the incidence and prevalence of HCC in patients with
HH and other liver diseases associated with iron overload are
discussed as well as the possible mechanisms for the increased risk
for hepatic carcinogenesis in these disorders.

PMID:15508107

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

Hepatocellular Iron Accumulation and Increased Cell Proliferation in
Polychlorinated Biphenyl-Exposed Sprague-Dawley Rats and the
Development of Hepatocarcinogenesis
Toxicol. Sci. (2001) 62 (1): 36-45.
J. Whysner1 and C.-X. Wang
American Health Foundation, 1 Dana Road, Valhalla, New York 10595
1.The major findings of this research were presented at the 39th
annual meeting of the Society of Toxicology, March 2000, Philadelphia,
PA.
Received February 1, 2001.
Accepted April 16, 2001.

Abstract
Polychlorinated biphenyls (PCBs) are liver-tumor promoters in rodents,
but the underlying mechanisms have not been fully elucidated.
Tissue sections from the PCB bioassay reported by Mayes et al. 1998,
Toxicol. Sci., 41–66, were evaluated by histopathological techniques
that included immunohistochemistry.
In females, and to a much lesser extent in males, iron accumulation in
hepatocytes was found at the 26th-week sacrifice, which was pronounced
in the mid- and high-dose Aroclor-1254 and -1260 groups.
At 52 weeks, large accumulations of iron were also present in Kupffer
cells of females, and dose-related increases in proliferating cell
nuclear antigen (PCNA) hepatocyte labeling indices were found in both
males and females. These changes preceded the formation of liver
tumors, which were not generally found until 78 weeks.
Glutathione S-transferase placental (GSTP) positive foci were present
at 52 weeks in high-dose Aroclor-1254 and -1260 female groups, and
small foci were found in some Aroclor 1254-exposed female rats at 26
weeks, along with centrilobular hepatocytes expressing GSTP.
The results of this study suggest that PCB-induced iron accumulation
in hepatocytes is an early event that may be related to tumor
formation, especially in female rats.
In both males and females, increases in cell proliferation at 52 weeks
were statistically significantly correlated with tumor incidences at
termination among the various PCB dosage groups.
Consequently, iron accumulations producing oxidative damage, and
enhanced cell proliferation resulting in tumor promotion may be
components in the mode of action for PCB-induced hepatocarcinogenesis
in rodents.

Key words
polychlorinated biphenylscell proliferationcarcinogenesis

doi: 10.1093/toxsci/62.1.36

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DEAD PEOPLE WALKING
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Post by ironjustice
Iron deprivation suppresses hepatocellular carcinoma growth in
experimental studies.
Clin Cancer Res. 2011 Nov 3.
Ba Q, Hao M, Huang H, Hou J, Ge S, Zhang Z, Yin J, Chu R, Jiang LH,
Wang F, Chen K, Liu H, Wang H.
Institute for Nutritional Sciences, Shanghai Institute of Biological
Sciences, Chinese Academy of Sciences.
Abstract
PURPOSE: Hepatocellular carcinoma (HCC) is the third most common cause
of cancer-related death and iron overload is a significant risk factor
in the development of HCC. In this study we investigated the potential
application of depriving iron by a novel iron chelator,
thiosemicarbazone-24 (TSC24), in HCC treatment.
EXPERIMENTAL DESIGN: Two HCC cell lines and HFE knockout (HFE-/-) mice
were used to determine iron chelation efficiency of TSC24. The
anticancer effects of TSC24 on HCC were analyzed in vitro and in
athymic xenograft mouse models.
RESULTS: Treatment with TSC24 significantly decreased the cellular
iron concentration in hepatoma cells and the serum iron concentration
in HFE-/- mice, by blocking iron uptake and interfering with normal
regulation of iron levels. Moreover, the viability of HCC cell lines
was reduced by TSC24. Confirming the mechanism of the agent, this
decrease in viability could be partially rescued by addition of
exogenous iron. TSC24 also suppressed tumor growth in athymic mice
bearing human HCC xenografts in a concentration dependent manner
without apparent toxicity in parallel with a decrease in the serum
iron level. Further studies revealed that TSC24 efficiently triggered
cell cycle arrest and apoptosis in Hep3B and HepG2 cell lines.
CONCLUSIONS: TSC24 is a potent iron chelator that suppresses human HCC
tumor growth by disrupting iron homeostasis, reducing available iron
and triggering cell cycle arrest and apoptosis, without apparent host
toxicity at effective doses. Thus, TSC24 shows great potential for the
treatment of HCC.
PMID:22052937
Who loves ya.
Tom
Jesus Was A Vegetarian!http://tinyurl.com/2r2nkh
Man Is A Herbivore!http://tinyurl.com/4rq595
DEAD PEOPLE WALKINGhttp://tinyurl.com/zk9fk