Search

Two rhodium(iii) complexes (Rh(OQ)3 (1) and Rh(BrQ)2(CH3OH)Cl (2), HOQ = 8-hydroxyquinoline, HBrQ = 5-bromo-8-hydroxyquinoline) of 8-hydroxylquinoline were synthesized and characterized. By MTT assay, the in vitro cytotoxicity of complexes 1 and 2, compared with HOQ, HBrQ and cisplatin, was evaluated towards a series of tumor cell lines as well as the normal liver cell line HL-7702. Complexes 1 and 2 showed higher cytotoxicity against the tested tumor cell lines than the corresponding ligands, among which T-24 was the most sensitive cell line for complexes 1 and 2 (IC50 = 13.42 μM for 1, 18.91 μM for 2). Compared with cisplatin, complex 1 exhibited higher cytotoxicity against T-24 cells but lower cytotoxicity against HL-7702(IC50 = 15.93 μM). Considering the better cytotoxicity of complex 1 than complex 2 against T-24 cells, the underlying anticancer molecular mechanisms were also investigated. DNA interaction studies revealed that complex 1 interacted with ct-DNA mainly via an intercalative binding mode. Further investigation of intracellular mechanisms revealed that complex 1 caused G2 phase cell cycle arrest and induced T-24 cell apoptosis in a dose-dependent mode. Targeting the mitochondrial pathway, the apoptotic mechanism in T-24 cells treated with 1 was studied by ROS detection, intracellular Ca2+ concentration measurements and caspase-9/3 activity assay, which suggested that complex 1 induced T-24 cell apoptosis by the disruption of mitochondrial-related mechanisms. [ABSTRACT FROM AUTHOR]

Complexes of yttrium(iii) and dysprosium(iii) with the traditional Chinese medicine active ingredient oxoglaucine (OG), namely [Y(OG)2(NO3)3]·CH3OH (1) and [Dy(OG)2(NO3)3]·H2O (2), were synthesized and characterized by elemental analysis, IR, ESI-MS, 1H and 13C NMR as well as single-crystal X-ray diffraction analysis. In vitro the complexes exhibited higher anticancer activity than the free ligand OG against the tested cancer cell lines. Among the tested cell lines, HepG2 is the most sensitive to the complexes. Complex 2 can trigger DNA damage in HepG2 cells, resulting in cell cycle arrest in the S phase and leading to cell apoptosis. The S phase cell-cycle arrest is caused via the ATM (ataxia-telangiectasia mutated)-Chk2-Cdc25A pathway. Chk2 is phosphorylated and activated in an ATM-dependent manner. It, in turn, phosphorylates Cdc25A phosphatise on serine124, causing the inactivation of Cdc25A in ubiquitin-mediated proteolytic degradation. The cyclin-Cdk complexes of the S phase could also be inhibited by limited supply of cyclins A and E. This irreversible cell cycle arrest process ultimately induces mitochondria-involved apoptotic cell death via the activation of Bcl-2 protein. Complex 2 effectively inhibited tumour growth in the BEL-7402 xenograft mouse model and exhibited higher safety in vivo than cisplatin. [ABSTRACT FROM AUTHOR]