RT Journal Article T1 Combined effect of caspase-dependent and caspase-independent apoptosis in the anticancer activity of gold complexes with phosphine and benzimidazole derivatives A1 Rouco Méndez, Lara A1 Sánchez González, María Ángeles A1 Alvariño Romero, Rebeca A1 Alfonso Rancaño, María Amparo A1 Vázquez López, Ezequiel Manuel A1 Garcia Martinez, Emilia A1 Maneiro Maneiro, Marcelino K1 2303 Química Inorgánica AB Since the potential anticancer activity of auranofin was discovered, gold compounds have attracted interest with a view to developing anticancer agents that follow cytotoxic mechanisms other than cisplatin. Two benzimidazole gold(I) derivatives containing triphenylphosphine (Au(pben)(PPh3)) (1) or triethylphosphine (Au(pben)(PEt3)) (2) were prepared and characterized by standard techniques. X-ray crystal structures for 1 and 2 were solved. The cytotoxicity of 1 and 2 was tested in human neuroblastoma SH-SY5Y cells. Cells were incubated with compounds for 24 h with concentrations ranging from 10 µM to 1 nM, and the half-maximal inhibitory concentration (IC50) was determined. 1 and 2 showed an IC50 of 2.7 and 1.6 µM, respectively. In order to better understand the type of cell death induced by compounds, neuroblastoma cells were stained with Annexin-FITC and propidium iodide. The fluorescence analysis revealed that compounds were inducing apoptosis; however, pre-treatment with the caspase inhibitor Z-VAD did not reduce cell death. Analysis of compound effects on caspase-3 activity and reactive oxygen species (ROS) production in SH-SY5Y cells revealed an antiproliferative ability mediated through oxidative stress and both caspase-dependent and caspase-independent mechanisms. PB Pharmaceuticals SN 14248247 YR 2020 FD 2020-12-24 LK http://hdl.handle.net/11093/2080 UL http://hdl.handle.net/11093/2080 LA eng NO Pharmaceuticals, 14(1): 10 (2020) NO Xunta de Galicia | Ref. ED431C 2017/01 DS Investigo RD 23-sep-2023