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• W1976937900 abstract "Desferrithiocin (DFT) is an orally effective Fe chelator, with a similar high affinity and selectivity for Fe to desferrioxamine (DFO), which has been shown clinically to possess antineoplastic activity. In this study, DFT was assessed for antineoplastic potential in hepatocellular carcinoma cell lines (HCC). This was done as there are few treatments for this aggressive neoplasm. The effects of DFT on cell proliferation, cell cycle progression, Fe uptake and toxicity were examined. To establish whether DFT was selective for cancer cells a comparison was made with normal (non‐proliferating) hepatocytes and non‐tumorigenic (proliferating) fibroblasts (SWISS‐3T3). DFT was a potent inhibitor of HCC proliferation (IC 50 ∼40 μ M ). DFO also inhibited HCC proliferation under the same conditions, but was much less active (IC 50 =110 – 210 μ M ). When saturated with Fe, the activity of DFT, like DFO, was greatly diminished, suggesting it may act by depriving the cells of Fe or inactivating essential Fe pool(s). Indeed DFT rapidly decreased Fe uptake from Tf‐ 59 Fe by hepatoma cells and also by normal hepatocytes. However, DFT (and DFO) had much less effect on cell survival in hepatocytes and fibroblasts than in hepatoma cells. DFT may, like DFO, inhibit the cell cycle in the S phase of DNA synthesis. Both chelators showed low toxicity. These results indicate that DFT has potent antineoplastic activity in HCC. Further investigation into the DFT class of Fe chelators seems warranted, particularly in view of its high activity in relation to DFO, a chelator which is already in clinical trial for neuroblastoma. British Journal of Pharmacology (2002) 135 , 1393–1402; doi: 10.1038/sj.bjp.0704507" @default.
• W1976937900 created "2016-06-24" @default.
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• W1976937900 date "2002-03-01" @default.
• W1976937900 modified "2023-10-07" @default.
• W1976937900 title "Desferrithiocin is a more potent antineoplastic agent than desferrioxamine" @default.
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• W1976937900 doi "https://doi.org/10.1038/sj.bjp.0704507" @default.
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