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Iron deprivation suppresses hepatocellular carcinoma growth in experimental studies.
MedLine Citation:
PMID:  22052937     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
Qian Ba; Miao Hao; He Huang; Junmei Hou; Shichao Ge; Zhuzhen Zhang; Jun Yin; Ruiai Chu; Liang Hua Jiang; Fudi Wang; Kaixian Chen; Hong Liu; Hui Wang
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-11-3
Journal Detail:
Title:  Clinical cancer research : an official journal of the American Association for Cancer Research     Volume:  -     ISSN:  1078-0432     ISO Abbreviation:  -     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-4     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9502500     Medline TA:  Clin Cancer Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Institute for Nutritional Sciences, Shanghai Institute of Biological Sciences, Chinese Academy of Sciences.
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