Sodium arsenite dependent protein expression analysis on human embryonic carcinoma (NCCIT) cell line

Abstract

Due to their pluripotent nature, embryonic carcinoma (EC) cell lines are useful for the study of basic and applied aspects of medical therapeutics, disease management and environmental mutagenesis. We evaluated the teratogenic like effects of inorganic arsenic during the early stages of cellular development in NCCIT cells, a type of human EC cells. Using matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and MetaCore pathway analysis software (GeneGo), the proteomic expression profiles of NCCIT cells after either short- or long-term sodium arsenite (NaAsO2) treatment and of NCCIT cell-derived embryoid bodies (EBs) after short-term NaAsO2 treatment were studied to determine the toxic effects on the process of normal growth and differentiation. The protein expression profiles of the NaAsO2-treated NCCIT cells and EBs were compared with that of untreated NCCIT cells. Short-term NaAsO2 treatment resulted in the down-regulation of most proteins, with heat shock 90-kDa protein (HSP90) and valosin-containing protein (VCP) being significantly downregulated. Long-term NaAsO2 treatment caused marked up-regulation of B23/nucleophosmin, glucose regulated protein 78-kDa (GRP78), unc-51-like kinase 3 (ULK3), toll-like receptor 6 precursor (TLR6) and mitogen-activated protein kinase 7 isoform A (MAP3K7). NaAsO2 treatment of the NCCIT cell-derived EBs resulted in the down-regulation of several tumor-suppressor proteins. Taken together, these data suggest that a wide spectrum of cellular responses is induced to cope with chronic non-lethal toxic stresses in NCCIT cells. (C) 2011 Elsevier Ireland Ltd. All rights reserved.