Ru(III) complexes with pyrazolopyrimidines as anticancer agents: bioactivities and the underlying mechanisms

Three ruthenium(III) complexes with pyrazolopyrimidine [Ru(L-n)(H2O)Cl-3] (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 (Delta Psi). 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.

Automated summary

The study demonstrated that three ruthenium(III) complexes exhibit strong anticancer effects, showing high cytotoxicity against SK-OV-3 cells and effective in vivo anticancer activity. The complexes induced apoptosis, cell cycle arrest, and DNA damage in cancer cells, highlighting their potential as promising anticancer agents.