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


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.


CONCLUSIONS
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.
Yoo
Dong Ryeol
DR
Gachon University of Medicine and Science, 534-2 Yeonsu-dong, Yeonsu-gu, Incheon, Republic of Korea.
Chong
Seon Ah
SA
Nam
Myeong Jin
MJ
D000970:Antineoplastic Agents / Q000494:pharmacology*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004249:DNA Damage; D006801:Humans; D008113:Liver Neoplasms / Q000737:chemistry* / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010087:Oxides / Q000494:pharmacology*; D020543:Proteome / Q000032:analysis*; D040901:Proteomics; D017382:Reactive Oxygen Species / Q000378:metabolism
D000970:Antineoplastic Agents; D001152:Arsenicals; D010087:Oxides; D020543:Proteome; D017382:Reactive Oxygen Species; D000077237:Arsenic Trioxide