“玫瑰树碱”衍生物对多种癌症有特别疗效

法国国家科研中心的研究人员日前通过实验发现，“玫瑰树碱”的衍生物对多种癌症具有特别疗效，这一发现将有助于抗癌新药的研发。

该研究由法国国家科研中心与法国原子能委员会、法国国家健康与医学研究所和居里大学等机构联合完成。研究人员在最新一期美国《癌症研究》上报告说，“玫瑰树碱”可从大洋洲一种常见玫瑰植株的叶子中提取，它通过破坏脱氧核糖核酸杀死癌细胞，功效显著。但与此同时，它攻击的目标性较差，会“误杀”不少健康细胞，从而带来严重的副作用。 

报告说，研究人员通过大量筛选，找到了“玫瑰树碱”的几种衍生物，这些衍生物对蛋白激酶CK2具有特别的功效。蛋白激酶在乳腺癌和前列腺癌等多种癌症的扩散中起着关键作用，如能抑制它的活性，治疗癌症事半功倍。研究人员随后在试管内和实验鼠身上进行了测试，都取得成功。

研究小组负责人克洛德·科歇表示，“玫瑰树碱”的这些衍生物能有效抑制肿瘤扩散，同时它们的目标性很强，产生的副作用比较小。这项研究成果将为癌症治疗开辟新途径。（生物谷Bioon.com）

生物谷推荐原文出处：

Cancer Research  doi: 10.1158/0008-5472.CAN-10-0917

Antitumor Activity of Pyridocarbazole and Benzopyridoindole Derivatives that Inhibit Protein Kinase CK2

Renaud Prudent1,2,3, Virginie Moucadel1,2,3, Chi-Hung Nguyen4, Caroline Barette5, Frédéric Schmidt6,7, Jean-Claude Florent6,7, Laurence Lafanechère5, Céline F Sautel1,2,3, Eve Duchemin-Pelletier1,2,3, Elodie Spreux1,2,3, Odile Filhol1,2,3, Jean-Baptiste Reiser8, and Claude Cochet1,2,3

Abstract
The alkyloid compound ellipticine derived from the berrywood tree is a topoisomerase II poison that is used in ovarian and breast cancer treatment. In this study, we report the identification of ellipticine derivatives and their tetracyclic angular benzopyridoindole analogues as novel ATP-competitive inhibitors of the protein kinase CK2. In vitro and in vivo assays showed that these compounds have a good pharmacologic profile, causing a marked inhibition of CK2 activity associated with cell cycle arrest and apoptosis in human cancer cells. Further, in vivo assays demonstrate antitumor activity in a mouse xenograft model of human glioblastoma. Finally, crystal structures of CK2–inhibitor complex provide structural insights on the molecular basis of CK2 inhibition. Our work lays the foundation for development of clinically useful CK2 inhibitors derived from a well-studied scaffold with suitable pharmacokinetics parameters.