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Issue 42, 2019
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A dual functional ruthenium arene complex induces differentiation and apoptosis of acute promyelocytic leukemia cells

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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

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Supplementary files

Article information


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

Chem. Sci., 2019,10, 9721-9728
Article type
Edge Article

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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