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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 RAR? genes is responsible for over 98% of cases of APL. In this work, we found that a Ru(ii) arene complex, [(?6-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-RAR? 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.

SUBMITTER: Huang H

PROVIDER: S-EPMC6993625 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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

Huang Hai H Cao Kaiming K Kong Yaqiong Y Yuan Siming S Liu Hongke H Wang Yucai Y Liu Yangzhong Y

Chemical science 20190828 42

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 ...[more]

PMID: 32055340

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

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

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