Surfactant 4-nonylphenyl-polyethylene glycol stimulates reactive oxygen species generation and apoptosis in human neuroblastoma cells

摘要

The formulation of most pesticides is proprietary and individual components are therefore not generally known. In a preliminary study, we identified six compounds that are often present in pesticides, of which 4-nonylphenyl-polyethylene glycol(NP-40) was found to be the most toxic. In this study, we investigated the toxicity of NP-40 and underlying mechanism in neuronal SK-N-SH cells. Exposure to NP 40 at concentrations higher than60 μmol/L for 24 hr decreased cell viability. The cytotoxicity of NP-40 was time-and concentration-dependent. Nuclear fragmentation and chromatin condensation were apparent starting at 50 μmol/L NP-40, and increased at higher concentrations. The expression of apoptotic factors including p53 and B-cell lymphoma(Bcl)-2-associated X protein was upregulated, while that of the anti-apoptotic marker Bcl-2 was downregulated at 80 μmol/L NP-40. Cytochrome c release was observed from 80 to 100 μmol/L by confocal microscopy. Caspase-9 and-3/7 activities increased according to concentration, and fluorescence-activated cell sorting analysis showed that apoptosis was induced at50 μmol/L and was increased at 80 μmol/L. Our findings indicate that NP-40 stimulates the mitochondrial-mediated apoptosis pathway and reactive oxygen species production in a concentration-dependent manner, and suggest that antioxidant administration may be an effective treatment for patients with acute NP-40 poisoning.