Issue 42, 2019

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

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, [(η6-p-bip)Ru(en)Cl][PF6] (Ru-1), 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, Ru-1 can also bind to DNA and trigger apoptosis of APL cells. Therefore, Ru-1 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 Ru-1 to PML suggests a new strategy for the development of anti-APL drugs using ruthenium agents.

Graphical abstract: A dual functional ruthenium arene complex induces differentiation and apoptosis of acute promyelocytic leukemia cells

Supplementary files

Article information

Article type
Edge Article
Submitted
23 Jun 2019
Accepted
28 Aug 2019
First published
28 Aug 2019
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2019,10, 9721-9728

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

H. Huang, K. Cao, Y. Kong, S. Yuan, H. Liu, Y. Wang and Y. Liu, Chem. Sci., 2019, 10, 9721 DOI: 10.1039/C9SC03110C

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