1. Ru(III) complexes with pyrazolopyrimidines as anticancer agents: bioactivities and the underlying mechanisms.
- Author
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Gu, Yun-Qiong, Shen, Wen-Ying, Yang, Qi-Yuan, Chen, Zhen-Feng, and Liang, Hong
- Subjects
CYCLIN-dependent kinases ,DNA topoisomerase I ,ANTINEOPLASTIC agents ,LIVER cells ,CYTOCHROME c ,CELL cycle - Abstract
Three ruthenium(III) complexes with pyrazolopyrimidine [Ru(L
n )(H2 O)Cl3 ] (1–3, n = 1–3) were prepared and characterized. These Ru(III) compounds show strong cytotoxicity against six cancer cell lines and low toxicity to normal human liver cells. Particularly, they exhibited stronger cytotoxicity to SK-OV-3 cells than cisplatin. Mechanism studies revealed that complex 1 inhibited tumor cell invasion and suppressed cell proliferation, induced apoptosis by elevating the levels of intracellular ROS (reactive oxygen species) and free calcium (Ca2+ ), and reduced mitochondrial membrane potential (ΔΨ). It also activated the caspase cascade, accompanied with upregulation of cytochrome c, Bax, p53, Apaf-1 and downregulation of Bcl-2. Moreover, complex 1 caused cell cycle arrest at S phase by inhibiting the expression of CDC 25, cyclin A2 and CDK 2 proteins, and induced DNA damage by interacting with DNA and inhibiting the topoisomerase I enzyme. Complex 1 exhibited efficient in vivo anticancer activity in a model of SK-OV-3 tumor xenograft. [ABSTRACT FROM AUTHOR]- Published
- 2022
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