Superoxide dismutase in gastric adenocarcinoma: is it a clinical biomarker in the development of cancer?

Abstract

Gastric cancer is the second most common cancer worldwide. The involvement of reactive oxygen species (ROS) in the pathogenesis of gastric malignancies is well known. Many human tumours have shown significant changes in the activity and expression of superoxide dismutase (SOD), which might be correlated with clinical-pathological parameters for the prognosis of human carcinoma. The aim of this study is the detection of MnSOD and CuZnSOD activity and their expression in gastric adenocarcinoma and healthy tissues. Gastric samples (adenocarcinoma and healthy tissues) harvested during endoscopy or resected during surgery were used to determine MnSOD and CuZnSOD activity and expression by spectrophotometric and Western blotting assays. The total SOD activity was significantly higher (p<0.05) in healthy mucosa with respect to gastric adenocarcinomas. No differences were found in MnSOD activity and, on the contrary, CuZnSOD activity was significantly lower (p<0.001) in cancer samples with respect to normal mucosa. The rate of MnSOD/CuZnSOD activity in adenocarcinoma was over ninefold higher than that registered in healthy tissues (p<0.05). Moreover, in adenocarcinoma MnSOD activity represented the 83% of total SOD with respect to healthy tissues where the ratio was 52% (p<0.001). On the contrary, in cancer tissues, CuZnSOD activity accounted for only 17% of the total SOD (p<0.001 if compared with the values recorded in normal mucosa). After immunoblotting, MnSOD was more expressed in adenocarcinoma with respect to normal mucosa (p<0.001), while CuZnSOD was similarly expressed in adenocarcinoma and healthy tissues. The SOD activity assay might provide a specific and sensitive method of analysis that allows the differentiation of healthy tissue from tumour tissue. The MnSOD to CuZnSOD activity ratio, and the ratio between these two isoforms and total SOD, presented in this preliminary study might be considered in the identification of cancerous from healthy control tissue.

Implications of antioxidant enzymes in human gastric neoplasms

“…Similar results were observed in our preliminary research (31), and these data are comparable to other studies in human colorectal (32) and in esophageal and gastric cancer which showed also a significant TNF-· increase (33). In this regard, MnSOD is characterized by low expression levels in cells, but can be strongly induced both in vivo and in vitro by multiple stress conditions, such as the presence of cytokines (such as TNF-· and interleukin-1), changes in cell redox state and hyperoxia (24).…”

“…Although several authors have considered this enzyme to be constitutively expressed, they revealed that its mRNA levels can be markedly up-and down-regulated by various physiological conditions such as the presence of hydrogen peroxide, arachidonic acid and heavy metals (31), as confirmed in the present study by the increase in Cu/ZnSOD expression in HP and cancer tissues. In agreement with these data, Matés and Sánchez-Jiménes (22) obtained similar results in cancer cells without the present characteristic trend between SOD isoforms.…”

“…Cu/ZnSOD expression generally is stable and its activity is considered to be an internal control for Cu/ZnSOD gene expression (31).…”

Aged black garlic extract induces inhibition of gastric cancer cell growth in�vitro and in�vivo

“…SOD activity was determined with the xanthine oxidasecytochrome c method according to a previous study (12). The cytochrome c reduction by superoxide anions generated by xanthine oxidase/hypoxanthine reaction was detected at 550 nm.…”

Genetic Bases for Predisposition to Common Multifactorial Disease in Man. Part I.

“…Mutations of the superoxide dismutase genes are considered to be associated with neoplastic and non-neoplastic diseases, as the involvement of reactive oxygen species (ROS) in the pathogenesis of malignancies and degenerative processes is well known (42,52,59). Low expression of MnSOD has been observed in different cancer tissues and several reports have shown that overexpression of MnSOD may inhibit growth in various human cancer cells.…”