Therapeutic Effect of Hydrogen Peroxide Via Altered Expression of Glutathione S-transferase and Peroxiredoxin-2 in Hepatocellular Carcinoma

Background: Hepatocellular carcinoma (HCC) has a high incidence and mortality that epitomizes one of the prominent causes of cancer-related death globally. Novel therapeutic approaches are therefore required. Reactive oxygen species (ROS) are necessary for maintaining cell cycle. Although ROS is involved in HCC progression, hydrogen peroxide (HO) has anti-proliferative effect on HCC.

Method: HCC Huh-7 cells were cultured and incubated with various concentrations of HO. Paraoxonase activity, levels of malondialdehyde, glutathione and protein oxidation were measured in treated and untreated Huh-7 cells. Furthermore, untreated and treated Huh-7 cells were subjected to two dimensional gel electrophoresis and identified protein spots which were differentially expressed by LC-MS/MS analysis. qRT-PCR was performed to validate the identified proteins.

Results: HO depleted glutathione (GSH) with the concomitant up-regulation of GSTP1 and Prx2. HO also increased malondialdehyde and protein oxidation, decreased the activity of paraoxonase in Huh-7 cells.

Conclusion: HO could be used as a novel therapeutic agent that might be beneficial in inducing cell cytotoxicity and hence suppress HCC proliferation.