Reactive oxygen species mediate arsenic induced cell transformation and tumorigenesis through Wnt/β-catenin pathway in human colorectal adenocarcinoma DLD1 cells.
Our study shows the following results: (1) selenite induced cancer cell death and apoptosis by producing superoxide radicals; (2) selenite-induced superoxide production, cell death, and apoptosis were inhibited by overexpression of MnSOD, but not by CuZnSOD, CAT, or GPx1; and (3) selenite treatment resulted in a decrease in mitochondrial membrane potential, release of cytochrome c into the cytosol, and activation of caspases 9 and 3, events that were suppressed by overexpression of MnSOD.
Specifically, we describe (1) the sources of free radicals occurring during exercise, (2) existing experimental data on physical exercise, lipid peroxidation and cancer, (3) existing supporting data implicating exercise-induced reactive oxygen species (ROS) as the mechanism responsible for increased apoptosis in different cell systems, and (4) changes in the antioxidant enzymes glutathione S transferases (GSTs), superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT) that occur after physical exercise, which are believed to be a physiologic response to oxidative stress induced by physical exercise.
The antioxidant enzymes, glutathione peroxidase (GPx), catalase and superoxide dismutases (SOD1, SOD2), have altered expression patterns in these cancer cell lines.
We hypothesized that inhibitors of peroxide removal, such as BCNU, an indirect inhibitor of glutathione peroxidase (GPx), and 3-amino-1,2,4-triazole (AT), a direct inhibitor of catalase (CAT), should cause toxicity to cancer cells after manganese superoxide dismutase (MnSOD) overexpression due to elevated peroxide levels.
Thus, inflammation in the lung may contribute to high levels of manganese SOD and decreased catalase, which together may lead to increased hydrogen peroxide intracellularly and create an intracellular environment favorable to DNA damage and the promotion of cancer.