Ru(III) complexes with pyrazolopyrimidines as anticancer agents: bioactivities and the underlying mechanisms.
Yun-Qiong GuWen-Ying ShenQi-Yuan YangZhen-Feng ChenHong LiangPublished in: Dalton transactions (Cambridge, England : 2003) (2022)
Three ruthenium(III) complexes with pyrazolopyrimidine [Ru(L n )(H 2 O)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 (Ca 2+ ), and reduced mitochondrial membrane potential (Δ Ψ ). 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.
Keyphrases
- induced apoptosis
- signaling pathway
- cell cycle arrest
- pi k akt
- oxidative stress
- cell death
- dna damage
- endoplasmic reticulum stress
- reactive oxygen species
- cell proliferation
- cell cycle
- diabetic rats
- poor prognosis
- energy transfer
- single cell
- drug induced
- protein kinase
- binding protein
- young adults
- squamous cell
- case control
- climate change