Fig. 1.Mechanism of redox balance–related HCC development. Both
mitochondrial electron leakage and oxidase (NOX, XO, and CYP450) enzyme activity
can produce superoxide anions (O). SOD converts
O into hydrogen peroxide (HO), which undergoes
conversion into HO through CAT and GPX [19]. During the GPX reaction, GSH
is oxidized to form GSSG, which can be reverted to GSH by GR following NADPH
consumption [20]. NASH can promote ROS production through increased fat
accumulation, which leads to the induction of OS. HBx in HBV and core proteins in
HCV can cause ROS accumulation. ROS can trigger apoptosis, cell necrosis, and
ferroptosis in liver cancer, but if the oxidant/antioxidant balance is disturbed,
it can cause accumulation in DNA mutations, promote genetic instability, and
result in liver cancer cell proliferation, metastasis, and drug resistance.
Abbreviations used: CAT, catalase; GPX, glutathione peroxidase; GR, glutathione
reductase; GSH, glutathione; GSSG, glutathione disulfide; HBV, hepatitis B virus;
HBx, hepatitis B virus x; HCC, hepatocellular carcinoma; HCV, hepatitis C virus;
NASH, nonalcoholic steatohepatitis; NOX, NADPH oxidase; ROS, reactive oxygen
species; SOD, superoxide dismutase; XO, xanthine oxidase.