RNA cleavage and inhibition of protein synthesis by bleomycin
RNA cleavage and inhibition of protein synthesis by bleomycin
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DOI：
10.1016/s1074-5521(02)00306-x
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发表时间：
2003-01-01
影响因子：
--
通讯作者：
Hecht, SM
中科院分区：
文献类型：
--
作者：
Abraham, AT;Lin, JJ;Hecht, SM
博来霉素是一种临床使用的抗肿瘤抗生素，长期以来被认为在 DNA 切割水平上发挥治疗作用。最近，人们已经清楚博来霉素还可以切割所有主要 RNA 类别的选定成员。使用计算机程序COMPARE搜索美国国家癌症研究所抗癌药物筛选计划建立的数据库，发现目前正在III期临床试验中评估的抗肿瘤核糖核酸酶onconase与化疗药物博来霉素之间可能存在基于机制的相关性。根据这些观察结果，实验表明，博莱霉素在兔网织红细胞裂解液中以及显微注射到非洲爪蟾卵母细胞中时，会引起 tRNA 裂解和 DNA 独立的蛋白质合成抑制。蛋白质合成抑制与先前报道的由博莱霉素引起的位点特异性RNA裂解的相关性支持这样的论点：RNA裂解可能构成博来霉素作用机制的重要元素。
Bleomycin is a clinically used antitumor antibiotic long thought to function therapeutically at the level of DNA cleavage. Recently, it has become clear that bleomycin can also cleave selected members of all major classes of RNA. Using the computer program COMPARE to search the database established by the Anticancer Drug Screening Program of the National Cancer Institute, a possible mechanism-based correlation was found between onconase, an antitumor ribonuclease currently being evaluated in phase III clinical trials, and the chemotherapeutic agent bleomycin. Following these observations, experimentation revealed that bleomycin caused tRNA cleavage and DNA-independent protein synthesis inhibition in rabbit reticulocyte lysate and when microinjected into Xenopus oocytes. The correlation of protein synthesis inhibition to the previously reported site-specific RNA cleavage caused by bleomycin supports the thesis that RNA cleavage may constitute an important element of the mechanism of action of bleomycin.