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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Cytotoxic activity of deferiprone, maltol and related hydroxyketones against human tumor cell lines.

Hydroxyketone chelators, deferiprone ( HK1), maltol (HK3) and their related compounds ( HK2, 4-8), were characterized for their cytotoxic profiles against oral human normal and tumor cells. Most hydroxyketones except HK6 showed relatively higher tumor-specific cytotoxicity. Deferiprone ( HK1), which showed the highest tumor specificity, had 10 times higher cytotoxicity than maltol (HK3) in both human promyelocytic leukemia HL-60 and human oral squamous cell carcinoma HSC-2 cell lines. The cytotoxic activity of HK1 against HL-60 and HSC-2 cells was reduced in the presence of FeCl3, while that of HK3 was significantly increased by FeCl3. Agarose gel electrophoresis showed that HK1 induced internucleosomal DNA fragmentation in HL-60 cells, but the addition of FeCl3 inhibited the DNA fragmentation. HK3 did not induce DNA fragmentation in HL-60 cells, regardless of the presence or absence of FeCl3. In HSC-2 cells, HK1 and 3 did not induce DNA fragmentation in the presence or absence of FeCl3. Colorimetric protease assay showed that HK1 activated the caspase 3, 8 and 9 in HL-60 cells. On the other hand, HK3 did not activate the caspase 3, 8 and 9 in HL-60 cells, but activated the caspase 3 only slightly in the presence of FeCl3. HK1 and 3 also activated the caspase 3, 8 and 9 in HSC-2 cells, but to a lesser extent. The present study suggested that the antitumor activity of hydroxyketones may be modified by Fe3+ concentration.[1]

References

  1. Cytotoxic activity of deferiprone, maltol and related hydroxyketones against human tumor cell lines. Yasumoto, E., Nakano, K., Nakayachi, T., Morshed, S.R., Hashimoto, K., Kikuchi, H., Nishikawa, H., Kawase, M., Sakagami, H. Anticancer Res. (2004) [Pubmed]
 
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