The Cell Killing Mechanisms of Hydroxyurea.
The Cell Killing Mechanisms of Hydroxyurea.
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作者：
Singh A;Xu YJ
羟基脲是一种成熟的核糖核苷酸还原酶抑制剂，在治疗肿瘤和非肿瘤疾病方面有着悠久的科学兴趣和临床应用。目前，它是治疗镰状细胞性贫血和慢性骨髓增生性疾病的主要药物。由于羟基脲对多种生物的DNA复制具有可逆的抑制作用，在实验室中也常用于细胞周期同步或产生复制应激。然而，高浓度的孵育或低剂量的羟基脲长期处理可导致细胞死亡，而在被阻止的复制分叉处产生的DNA损伤通常被认为是直接原因。最近对多种模式生物的研究表明，氧化应激和其他几种机制可能是羟基脲的大部分细胞毒性作用的原因。本文就羟基脲杀伤细胞机制的研究进展进行综述，以期为改进羟基脲类药物的化疗提供新的思路。
Hydroxyurea is a well-established inhibitor of ribonucleotide reductase that has a long history of scientific interest and clinical use for the treatment of neoplastic and non-neoplastic diseases. It is currently the staple drug for the management of sickle cell anemia and chronic myeloproliferative disorders. Due to its reversible inhibitory effect on DNA replication in various organisms, hydroxyurea is also commonly used in laboratories for cell cycle synchronization or generating replication stress. However, incubation with high concentrations or prolonged treatment with low doses of hydroxyurea can result in cell death and the DNA damage generated at arrested replication forks is generally believed to be the direct cause. Recent studies in multiple model organisms have shown that oxidative stress and several other mechanisms may contribute to the majority of the cytotoxic effect of hydroxyurea. This review aims to summarize the progress in our understanding of the cell-killing mechanisms of hydroxyurea, which may provide new insights towards the improvement of chemotherapies that employ this agent.
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