Effects of bortezomib on intracellular antioxidant and apoptosis in HepG2cells.

Bortezomib, as a proteasome inhibitor, is used in clinical trials related to solid cancers. However, its use is not always associated with a good response to treatment. Taking into account the above, we decided to analyze the effect of the time-dependency (24 vs. 48 h) and the dose-dependency of bortezomib (2, 4, 8 and 16 nM) on apoptosis and activities of antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR), glutathione peroxidase (GPx) and glutathione transferase (GST), as well as concentrations of reduced glutathione (GSH) and malondialdehyde (MDA) in hepatoblastoma cell line (HepG2) cells. We have shown that increasing concentrations of bortezomib caused (I) a gradual decrease in the levels of GSH; (II) changes in MDA concentrations and antioxidant enzymes activities; (III) increase in apoptosis levels in HepG2 cells. We did not find significant association between antioxidant parameters and number of apoptotic cells. Our study showed that the analyzed parameters (such as: CAT, SOD, GR, GPx, GST, GSH, MDA) changed after bortezomib treatment. It is important to search for new anti-cancer therapies based on next-generation proteasome inhibitors. It is possible that the use of proteins associated with oxidative stress will help enhance the action of these inhibitors and will provide a better treatment effect.