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

Alarifi, Saud; Ali, Daoud; Alkahtani, Saad; Siddiqui, Maqsood A.; Ali, Bahy A.
February 2013
OncoTargets & Therapy;2013, Vol. 6, p75
Academic Journal
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 sress.


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