Mechanism of antineuroblastoma activity of deferoxamine in vitro.
Mechanism of antineuroblastoma activity of deferoxamine in vitro.
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发表时间：
1988-10
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通讯作者：
J. Blatt;S. Taylor;S. Stitely
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作者：
J. Blatt;S. Taylor;S. Stitely
去铁胺先前已被证明在体外对人神经母细胞瘤细胞具有有效活性，该活性源于其螯合铁的能力。为了进一步了解去铁胺诱导细胞毒性的机制，我们通过CHP 126观察了其对细胞周期以及DNA、RNA和蛋白质合成的影响，CHP 126是一种来源于神经母细胞瘤患者肿瘤组织的细胞系，已知其对药物敏感。暴露于60 mumol/L去铁胺24小时后，细胞周期的非增殖期和复制前期的细胞百分比增加35%，细胞周期的DNA合成期、复制后期和有丝分裂期的细胞百分比相应减少，结果与早期DNA合成期细胞周期进展阻滞一致。通过证明CHP 126短期培养物中胸苷掺入DNA减少60%，证实了去铁胺对DNA合成的抑制作用。对RNA和蛋白质合成的影响极小。通过使用与不同铁池相互作用的几种螯合剂，观察到对生长的等效作用，这表明细胞内和细胞外铁都是神经母细胞瘤细胞生长所需的。
Deferoxamine previously has been shown to have potent activity in vitro against human neuroblastoma cells, activity that results from its ability to chelate iron. To further understand the mechanism of deferoxamine-induced cytotoxicity, we looked at its effects on cell cycling and on DNA, RNA, and protein synthesis by CHP 126, a cell line that is derived from tumor tissue of a patient with a neuroblastoma and that is known to be drug sensitive. After 24 hours of exposure to 60 mumol/L deferoxamine, there was a 35% increase in the percent of cells in the nonproliferating and prereplicative phases of the cell cycle and a corresponding decrease in the percent of cells in the DNA synthesis, postreplicative, and mitotic phases of the cell cycle, results that are consistent with a block of cell cycle progression at the early DNA synthesis phase. The inhibitory effects of deferoxamine on DNA synthesis were confirmed by demonstration of a 60% decrease in thymidine incorporation into DNA in short-term cultures of CHP 126. Effects on RNA and protein synthesis were minimal. Equivalent effects on growth were seen by using several chelators that interact with different iron pools, suggesting that both intracellular and extracellular iron are required for growth of neuroblastoma cells.