Desferrithiocin is a more potent antineoplastic agent than desferrioxamine

British Journal of Pharmacology
A KicicErica Baker

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) approximately 40 microM). DFO also inhibited HCC proliferation under the same conditions, but was much less active (IC(50)=110 - 210 microM). 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 hepatom...Continue Reading

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Citations

Oct 6, 2007·Biological Trace Element Research·Kurinchi Gurusamy
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