Pro-oxidant enzymes, redox balance and oxidative damage to proteins, lipids and DNA in colorectal cancer tissue. Is oxidative stress dependent on tumour budding and inflammatory infiltration?

Abstract

This study is the first to assess redox homeostasis in patients with colorectal cancer (CRC) in respect to histopathological parameters associated with the tumour microenvironment such as tumour budding and inflammatory infiltration. Pro-oxidant enzymes (NADPH oxidase (NOX), xanthine oxidase (XO)), antioxidant barrier (Cu,Zn-superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), reduced glutathione (GSH)), redox status (total antioxidant (TAC)/oxidant status (TOS)) and oxidative damage products (advanced glycation end products (AGE), advanced oxidation protein products (AOPP), malondialdehyde (MDA) and 8-hydroxydeoxyguanosine (8-OHdG)) were determined in both the normal and cancerous tissue of 29 CRC patients. The activity of NOX (p < 0.01) and XO (p = 0.01), as well as SOD (p < 0.0001), CAT (p < 0.0001) and TAC level (p < 0.01) were significantly higher in tumour tissue than in normal colon mucosa. Oxidative damage products (AGE—p < 0.01, AOPP—p < 0.001, MDA—p < 0.001, 8-OHdG—p < 0.0001) were also higher in cancerous colon tissue. Furthermore, we observed that CAT (p < 0.05) and XO (p < 0.05) activity depends on the intensity of inflammatory infiltration. Oxidative stress index (OSI) (p < 0.05) and MDA (p < 0.01) values were significantly higher in patients with tumour budding (TB) > 5 versus cases with TB < 5. However, OSI level did not differ significantly between cancer and normal tissue. Our results confirm that CRC is associated with enzymatic/non-enzymatic redox imbalance and increased oxidative damage to proteins, lipids and DNA. The determination of these biomarkers could be useful for the evaluation of the tumour progression.