Cell cycle synchronization and growth inhibition by 3-hydroxypyridin-4-one iron chelators in leukemia cell lines.
Cell cycle synchronization and growth inhibition by 3-hydroxypyridin-4-one iron chelators in leukemia cell lines.
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发表时间：
1992-09
期刊：
影响因子：
11.2
通讯作者：
K. P. Hoyes;R. Hider;J. Porter
中科院分区：
文献类型：
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作者：
K. P. Hoyes;R. Hider;J. Porter
在K562和Daudi细胞中，比较了双齿3-羟基吡啶-4-酮（HPO）铁螯合剂与六齿去铁胺（DFO）对细胞周期阻滞和随后周期同步的影响。探讨了螯合剂浓度与生长抑制、DNA合成和核糖核苷酸还原酶抑制、细胞周期阻滞期的关系。HPOs和DFO以剂量依赖的方式阻滞细胞周期，在浓度超过30微米铁结合当量的情况下，24小时后在G1-S边界造成阻断。这与核糖核苷酸还原酶活性降低以及DNA合成和生长的同时停止有关。当螯合剂随后被移除时，hpo处理的细胞同步级联进入S期，不像dfo处理的细胞以不同步的方式恢复循环。在K562和Daudi细胞中，约25微米和3微米铁结合当量的螯合剂浓度分别抑制了50%的生长、DNA合成和核糖核苷酸还原酶活性。低于10微米铁结合当量的浓度抑制了K562细胞的生长，对DNA合成没有影响，但在G2和M期细胞积累。这些结果表明，HPOs作为细胞周期同步剂比DFO有优势，可能是细胞周期特异性治疗方案的有用辅助物。
The effect of bidentate 3-hydroxypyridin-4-one (HPO) iron chelators on cell cycle arrest with subsequent cycle synchronization has been compared with that of the hexadentate desferrioxamine (DFO) in K562 and Daudi cells. The relationships between chelator concentration and inhibition of growth, DNA synthesis and ribonucleotide reductase, and phase of cell cycle arrest have also been explored. HPOs and DFO arrest the cell cycle in a dose-dependent manner causing a blockade at the G1-S border after 24 h at concentrations above 30 microM iron-binding equivalents. This is associated with reduced ribonucleotide reductase activity and concomitant cessation of DNA synthesis and growth. When the chelator is subsequently removed, HPO-treated cells synchronously cascade into S phase, unlike DFO-treated cells which resume cycling in a nonsynchronous manner. Chelator concentrations of approximately 25 microM and 3 microM iron-binding equivalents inhibited growth, DNA synthesis, and ribonucleotide reductase activity by 50% in K562 and Daudi cells, respectively. Concentrations less than 10 microM iron-binding equivalents inhibited K562 cell growth without an effect on DNA synthesis but with accumulation of cells in G2 and M phases. These results suggest that HPOs have advantages over DFO as cell cycle synchronization agents and may be useful adjuncts in cell cycle-specific treatment regimens.