一种双功能钌芳烃配合物可诱导急性早幼粒细胞白血病细胞分化和凋亡。

A dual functional ruthenium arene complex induces differentiation and apoptosis of acute promyelocytic leukemia cells.

作者信息

Huang Hai, Cao Kaiming, Kong Yaqiong, Yuan Siming, Liu Hongke, Wang Yucai, Liu Yangzhong

机构信息

CAS Key Laboratory of Soft Matter Chemistry , Department of Chemistry , University of Science and Technology of China , Hefei , Anhui 230026 , China . Email:

Jiangsu Key Laboratory of Biofunctional Materials , College of Chemistry and Materials Science , Nanjing Normal University , Nanjing , Jiang Su 210046 , China.

出版信息

Chem Sci. 2019 Aug 28;10(42):9721-9728. doi: 10.1039/c9sc03110c. eCollection 2019 Nov 14.

DOI:10.1039/c9sc03110c

PMID:32055340

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6993625/

Abstract

Human acute promyelocytic leukemia (APL) is the most malignant form of acute leukemia. The fusion of PML and RARα genes is responsible for over 98% of cases of APL. In this work, we found that a Ru(ii) arene complex, [(η--bip)Ru(en)Cl][PF] (), can selectively react with PML, leading to zinc-release and protein unfolding. Consequently, the degradation of the fusion protein PML-RARα occurs, which causes the differentiation of APL cells. In addition, can also bind to DNA and trigger apoptosis of APL cells. Therefore, acts as a dual functional agent that inhibits the growth of APL cells and induces cell differentiation. In contrast, the other non-selective Ru(ii) compound, though also highly reactive to PML, does not exhibit anti-APL activity. The selectivity of to PML suggests a new strategy for the development of anti-APL drugs using ruthenium agents.

摘要

人类急性早幼粒细胞白血病（APL）是急性白血病中最恶性的形式。PML和RARα基因的融合导致了超过98%的APL病例。在这项工作中，我们发现一种钌（II）芳烃配合物，[(η--联苯)Ru(en)Cl][PF]（），可以与PML选择性反应，导致锌释放和蛋白质解折叠。因此，融合蛋白PML-RARα发生降解，从而引起APL细胞的分化。此外，还可以与DNA结合并触发APL细胞的凋亡。因此，作为一种双功能剂，可抑制APL细胞的生长并诱导细胞分化。相比之下，另一种非选择性钌（II）化合物虽然对PML也具有高反应性，但不表现出抗APL活性。对PML的选择性为使用钌试剂开发抗APL药物提出了一种新策略。