A dual functional ruthenium arene complex induces differentiation and apoptosis of acute promyelocytic leukemia cells.
Hai HuangKaiming CaoYaqiong KongSiming YuanHong-Ke LiuYu-Cai WangYang-Zhong LiuPublished in: Chemical science (2019)
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.
Keyphrases
- cell cycle arrest
- induced apoptosis
- cell death
- endoplasmic reticulum stress
- energy transfer
- pi k akt
- liver failure
- endothelial cells
- bone marrow
- magnetic resonance imaging
- signaling pathway
- computed tomography
- dna methylation
- magnetic resonance
- respiratory failure
- intensive care unit
- small molecule
- genome wide
- water soluble
- acute respiratory distress syndrome
- cell free
- pluripotent stem cells
- protein protein