title: Iron deprivation suppresses hepatocellular carcinoma growth in experimental studies.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai, China.
authors: Qian
authors: Q
authors: Ba
authors: Miao
authors: M
authors: Hao
authors: He
authors: H
authors: Huang
authors: Junmei
authors: J
authors: Hou
authors: Shichao
authors: S
authors: Ge
authors: Zhuzhen
authors: Z
authors: Zhang
authors: Jun
authors: J
authors: Yin
authors: Ruiai
authors: R
authors: Chu
authors: Hualiang
authors: H
authors: Jiang
authors: Fudi
authors: F
authors: Wang
authors: Kaixian
authors: K
authors: Chen
authors: Hong
authors: H
authors: Liu
authors: Hui
authors: H
authors: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D057809:HEK293 Cells; D000071020:Hemochromatosis Protein; D056945:Hep G2 Cells; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D007501:Iron / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D007502:Iron Chelating Agents / Q000737:chemistry / Q000494:pharmacology*; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics; D051379:Mice; D057507:Mice, 129 Strain; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008819:Mice, Nude; D015394:Molecular Structure; D013882:Thiosemicarbazones / Q000737:chemistry / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: C549333:2-(quinolin-2-ylmethylene)hydrazinecarbothioamide; D051017:Apoptosis Regulatory Proteins; D000071020:Hemochromatosis Protein; C499535:Hfe protein, mouse; D015395:Histocompatibility Antigens Class I; D007502:Iron Chelating Agents; D008565:Membrane Proteins; D013882:Thiosemicarbazones; D007501:Iron