Iron Deprivation Suppresses Hepatocellular Carcinoma Growth in Experimental Studies

doi:10.1158/1078-0432.CCR-10-3099

	Iron Deprivation Suppresses Hepatocellular Carcinoma Growth in Experimental Studies
	Ba, Qian 2; Hao, Miao 2; Huang, He 1; Hou, Junmei 2; Ge, Shichao 2; Zhang, Zhuzhen 2; Yin, Jun 2; Chu, Ruiai 2; Jiang, Hualiang1 ; Wang, Fudi 2
刊名	CLINICAL CANCER RESEARCH
	2011-12-15
卷号	17 期号:24 页码:7625-7633
ISSN号	1078-0432
DOI	10.1158/1078-0432.CCR-10-3099
文献子类	Article
英文摘要	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. Clin Cancer Res; 17(24); 7625-33. (C)2011 AACR.
资助项目	Chinese Academy of Sciences[00000000] ; National Nature Science Foundation[81125020] ; National Nature Science Foundation[91029715] ; National Nature Science Foundation[31070680] ; National Nature Science Foundation[30870513] ; National Nature Science Foundation[81025017] ; Ministry of Science and Technology of China[2009CB919001] ; Ministry of Science and Technology of China[2012BAK01B04] ; Science and Technology Commission of Shanghai Municipality[08391910800] ; Science and Technology Commission of Shanghai Municipality[10391902100] ; Science and Technology Commission of Xuhui District of Shanghai Municipality[RCT201001] ; Science and Technology Commission of Xuhui District of Shanghai Municipality[CRC2010002] ; Director Foundation of INS[20090101] ; Food Safety Research Center[00000000] ; Key Laboratory of Nutrition and Metabolism of INS, SIBS, CAS[00000000]
WOS关键词	TOPOISOMERASE II-ALPHA ; CELL-CYCLE ; CANCER ; OVERLOAD ; CHELATORS ; DISEASE ; HEMOCHROMATOSIS ; RISK ; CARCINOGENESIS ; PROLIFERATION
WOS研究方向	Oncology
语种	英语
出版者	AMER ASSOC CANCER RESEARCH
WOS记录号	WOS:000298410300014
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/278302]
专题	药物化学研究室药物发现与设计中心
通讯作者	Wang, Hui
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 2.Chinese Acad Sci, Inst Nutr Sci, Shanghai Inst Biol Sci, Key Lab Nutr & Metab, Shanghai 200031, Peoples R China;
推荐引用方式 GB/T 7714	Ba, Qian,Hao, Miao,Huang, He,et al. Iron Deprivation Suppresses Hepatocellular Carcinoma Growth in Experimental Studies[J]. CLINICAL CANCER RESEARCH,2011,17(24):7625-7633.
APA	Ba, Qian.,Hao, Miao.,Huang, He.,Hou, Junmei.,Ge, Shichao.,...&Wang, Hui.(2011).Iron Deprivation Suppresses Hepatocellular Carcinoma Growth in Experimental Studies.CLINICAL CANCER RESEARCH,17(24),7625-7633.
MLA	Ba, Qian,et al."Iron Deprivation Suppresses Hepatocellular Carcinoma Growth in Experimental Studies".CLINICAL CANCER RESEARCH 17.24(2011):7625-7633.