Anti-tumor and cellular mechanisms of HfIV tetra-(8-hydroxyquinolinato) complexes

作者：Tiankun Zhao, Dikui Mei, Jing Ma, Nan Liu, Qi Zhang, Zhongduo Yang, Isabel Correia · 发表于：Journal of Inorganic Biochemistry · 年份：2025 · DOI：10.1016/j.jinorgbio.2025.112945 · 被引用次数：1 · 研究领域：Metal complexes synthesis and properties、Lanthanide and Transition Metal Complexes、Synthesis and Characterization of Heterocyclic Compounds

Three 8-hydroxyquinoline-stabilized hafnium complexes, [Hf IV (oxinate) 4 ] , were synthesized with good aqueous stability and solubility by reacting Hf IV Cl 4 with 8-hydroxyquinoline (HL 1 ), 2-methyl-8-hydroxyquinoline (HL 2 ) and 5-chloro-8-hydroxyquinoline (HL 3 ) in THF, achieving high yields. Among the synthesized complexes, [Hf IV (L 1 ) 4 ] and [Hf IV (L 3 ) 4 ] exhibited potent inhibitory activity against human liver (Hep G2), cervical (HeLa S3) and lung (PC9) cancer cell lines, while showing low toxicity against non-tumorigenic murine epithelial AML12 cells. Notably, [Hf IV (L 1 ) 4 ] demonstrated the most potent activity, with an IC 50 value of 0.8 ± 0.3 μM against Hep G2 cells, which is 17 times lower than that of cisplatin (IC 50 = 13.8 ± 1.3 μM). Mechanistic cell studies revealed that [Hf IV (L 1 ) 4 ] could effectively inhibit cell migration, induce reactive oxygen species generation and cause mitochondrial membrane potential disruption. Furthermore, [Hf IV (L 1 ) 4 ] blocked the cell cycle progression at the G2/M phase and led almost exclusively to early apoptosis in Hep G2 cells. Western blot analysis revealed that in Hep G2 cells [Hf IV (L 1 ) 4 ] could upregulate the expression of caspase-3 and Bax proteins while downregulating the expression of the anti-apoptotic Bcl-2 protein, highlighting the apoptotic pathway as a key mechanism of action. Comparisons are made with previously reported [Zr IV (L 1 ) 4 ] , which shows higher cytotoxicity, cellular uptake,...