Arsenic trioxide-mediated oxidative stress and genotoxicity in human hepatocellular carcinoma cells

rsenic trioxide-mediated oxidative stress and genotoxicity in human hepatocellular carcinoma cells Original Research (690) Total Article Views Authors: Alarifi S, Ali D, Alkahtani S, Siddiqui MA, Ali BA Published Date February 2013 Volume 2013:6 Pages 75 - 84 DOI: http://dx.doi.org/10.2147/OTT.S38227 Received: 17 September 2012 Accepted: 20 November 2012 Published: 07 February 2013 Saud Alarifi,1 Daoud Ali,1 Saad Alkahtani,1 Maqsood A Siddiqui,2 Bahy A Ali2,3 1Cell and Molecular Laboratory, Department of Zoology, Faculty of Science, King Saud University, Riyadh, Saudi Arabia; 2DNA Research Chair, Department of Zoology, Faculty of Science, King Saud University, Riyadh, Saudi Arabia; 3Genetic Engineering & Biotechnology Research Institute City for Scientific Research and Technology Applications, Alexandria, Egypt Background: Arsenic is a ubiquitous environmental toxicant, and abnormalities of the skin, lung, kidney, and liver are the most common outcomes of long-term arsenic exposure. This study was designed to investigate the possible mechanisms of genotoxicity induced by arsenic trioxide in human hepatocellular carcinoma cells. Methods and results: A mild cytotoxic response of arsenic trioxide was observed in human hepatocellular carcinoma cells, as evident by (3-(4,5-dimethyl thiazol-2-yl)-2, 5-diphenyl tetrazolium bromide) and lactate dehydrogenase assays after 24 and 48 hours of exposure. Arsenic trioxide elicited a significant (P < 0.01) reduction in glutathione (15.67% and 26.52%), with a concomitant increase in malondialdehyde level (67.80% and 72.25%; P < 0.01), superoxide dismutase (76.42% and 81.09%; P < 0.01), catalase (73.33% and 76.47%; P < 0.01), and reactive oxygen species generation (44.04% and 56.14%; P < 0.01) after 24 and 48 hours of exposure, respectively. Statistically significant (P < 0.01) induction of DNA damage was observed by the comet assay in cells exposed to arsenic trioxide. It was also observed that apoptosis occurred through activation of caspase-3 and phosphatidylserine externalization in human hepatocellular carcinoma cells exposed to arsenic trioxide. Conclusion: The results demonstrate that arsenic trioxide induces apoptosis and genotoxicity in human hepatocellular carcinoma cells through reactive oxygen species and oxidative stress.