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. 2025 Apr 28:13:e19235.
doi: 10.7717/peerj.19235. eCollection 2025.

Effects of bortezomib on intracellular antioxidant and apoptosis in HepG2cells

Grażyna Świderska-Kołacz  1 , Magdalena Madej  1 , Szymon Zmorzynski  2 , Wojciech Styk  3 , Iwona Surowiec  1 , Bożena Witek  1 , Anna Wojciechowska  4 , Joanna Czerwik-Marcinkowska  1 , Anna Nowakowska  5
Affiliations

Effects of bortezomib on intracellular antioxidant and apoptosis in HepG2cells

Grażyna Świderska-Kołacz et al. PeerJ. .

Abstract

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.

Keywords: Apoptosis; Bortezomib; HepG2 cells; Oxidative stress.

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Conflict of interest statement

The authors declare there are no competing interests.

Figures

Figure 1
Figure 1. Flow cytometry analysis of apoptosis in HepG2 cells treated with 2 nM and 16 nM of bortezomib.
Control for (A) 24 h; (B) 48 h; the cells treated with 2 nM of bortezomib for (C) 24 h, (D) 48 h; and 16 nM of bortezomib (C) for 24 h and, (D) 48 h.
Figure 2
Figure 2. The cell viability obtained by MTT after 24 (green) and 48 (blue) h of treatment with bortezomib.
(A) The cell viability obtained by MTT after 24 h of treatment with bortezomib. (B) The cell viability obtained by MTT after 48 h of treatment with bortezomib.
Figure 3
Figure 3. The cell viability obtained by MTT after 24 and 48 h of treatment with bortezomib.
(A) The cell viability obtained by MTT after 24 h of treatment with bortezomib. (B) The cell viability obtained by MTT after 48 h of treatment with bortezomib.
Figure 4
Figure 4. Canonical correspondence analysis.
Canonical correspondence analysis of data on the dependence of apoptosis rate on time and bortezomib concentration. Variables significant for the variability in the data set are marked in red (Monte Carlo Permutation Test, p < 0.05).
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