Proteome profiling of arsenic trioxide-treated human hepatic cancer cells.

Abstract

BACKGROUND: Arsenic trioxide (As(2)O(3)), a major compound in traditional Chinese medicine, is known to be an effective anticancer agent in acute promyelocytic leukemia (APL). The effects of As(2)O(3) on human hepatocellular carcinoma (HCC) SK-Hep-1 cells were studied employing proteomics-based methodologies. MATERIALS AND METHODS: Using 1-dimensional electrophoresis (1DE) and liquid chromatography electrospray ionization quadruple time-of-flight analysis, the whole proteomes of the control and As(2)O(3)-treated cells were profiled. RESULTS: In all, 207 and 62 proteins, which were specifically found in control and As(2)O(3)-treated cells, respectively, were classified with their biological processes by gene ontology (GO) annotation. The GO data indicated that 16 proteins were closely associated with apoptotic mechanisms. As(2)O(3)-induced DNA damage and oxidative stress that accompanied apoptosis in SK-Hep-1 cells were observed using comet assay and 5-and-6-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate fluorescence microscopy, respectively. CONCLUSION: The anticancer activities of As(2)O(3) may be mediated by DNA damage- and reactive oxygen species-induced apoptotic mechanisms which involve the proteins identified in this study.