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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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Publication details

The article was received on 23 Jun 2019, accepted on 28 Aug 2019 and first published on 28 Aug 2019


Article type: Edge Article
DOI: 10.1039/C9SC03110C
Chem. Sci., 2019, Advance Article
  • Open access: Creative Commons BY-NC license
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    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, Advance Article , DOI: 10.1039/C9SC03110C

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