A dual functional ruthenium arene complex induces differentiation and apoptosis of acute promyelocytic leukemia cells. Issue 42 (5th September 2019)

• Record Type: Journal Article
• Authors: Huang, Hai; Cao, Kaiming; Kong, Yaqiong; Yuan, Siming; Liu, Hongke; Wang, Yucai; Liu, Yangzhong
• Is Part Of: Chemical science. Volume 10:Issue 42(2019)
• Page Start: 9721
• Page End: 9728
• Publication Date: 2019-09-05
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/c9sc03110c
• Languages: English
• ISSNs: 2041-6520

Abstract

Abstract : A dual functional ruthenium arene complex induces differentiation and apoptosis of acute promyelocytic leukemia cells through degradation of PML–RARα and DNA damage. 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, [(η 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–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.