Eukaryotic translation initiation factor 4E (eIF4E) is a cellular target for cadmium toxicity.
Toxicologist 2004 Mar; 78(S-1):55-56
Cadmium, to which large numbers of people are occupationally and otherwise exposed, has been categorized as a human carcinogen by the International Agency for Research on Cancer (IARC). Several theories have been proposed to account for the mechanisms potentially responsible for cadmium toxicity and carcinogenesis. Recently, our laboratory has demonstrated a novel mechanism for cadmium carcinogenesis that involves the upregulation of translation initiation factor 3 and translation elongation factor-1 delta. Presently, we have investigated whether the translational proto-oncogene, eukaryotic initiation factor 4E (eIF4E) is a cellular target for cadmium toxicity and carcinogenesis. Four different human cell lines: HCT-15 (colorectal adenocarcinoma), PLC/PRF/5 (hepatocellular carcinoma), HeLa (adenocarcinoma) and Chang (likely derived from HeLa cells) cells, were exposed to 30 uM cadmium chloride for time intervals up to 24-hours and the expression level of eIF4E was determined by Western blot analysis using an antibody against human eIF4E. Exposure to 30 uM cadmium chloride resulted in significant cytotoxicity and cell death in all four cell lines tested. Furthermore, exposure to cadmium chloride resulted in significant inhibition of eIF4E in all cell lines, and the highest inhibition was noticed following the 24-hours exposure to cadmium chloride. The significance of cadmium chloride-mediated inhibition of eIF4E was further investigated by silencing the expression of eIF4E by employing small interfering RNA (SiRNA) specifically targeting eIF4E. The SiRNA mediated silencing of eIF4E resulted in significant cell death. Our results thus suggest that eIF4E is a cellular target for cadmium toxicity and that the cadmium-induced cytotoxicity and cell death may be due to the inhibition of eIF4E.
Cadmium-compounds; Occupational-exposure; Carcinogens; Toxins; Toxic-effects; Laboratory-testing; Chlorides; Cytotoxicity
Research Tools and Approaches: Cancer Research Methods
The Toxicologist. Society of Toxicology 43nd Annual Meeting and ToxExpo, March 21-25, 2004, Baltimore, Maryland