A bioinformatics analysis of clinical cancer genomic data revealed that matrix metalloproteinase (MMP)1 and three markers of oxidative stress - superoxide dismutase 2, NADPH oxidase 4, and carbonic anhydrase 9 - are upregulated in human mesenchymal GBM cancer tissue, and that MMP1 is positively correlated to all three of these oxidative stress markers.
4-Acetyl-Antroquinonol B Suppresses SOD2-Enhanced Cancer Stem Cell-Like Phenotypes and Chemoresistance of Colorectal Cancer Cells by Inducing hsa-miR-324 re-Expression.
To enable correct interpretation of active FOXO in cancer tissue, threshold levels for normal SOD2 expression in healthy tissue were defined above which FOXO activity is oxidative stress induced and below which PI3K regulated.
Furthermore, SOD1 activity, CS activity, SOD1 expression, GPX4 expression, and GPX4 protein level were inversely correlated with the malignancy, whereas catalase activity, catalase protein, SOD2 protein level, and the SOD2:CS ratio were positively correlated with the degree of malignancy.
Experimental and epidemiological evidence supporting a conflicting role of SOD2 in tumor biology, and epidemiological evidence that SOD2 and GPX1 can interact to affect cancer risk and progression indicated that it is the net accumulation of mitochondrial H<sub>2</sub>O<sub>2</sub> (mtH<sub>2</sub>O<sub>2</sub>) resulting from of the balance between the activities SOD2 and anti-oxidants such as GPX1 that determines whether SOD2 prevents or promotes oncogenesis.
Acquired Mitochondrial Abnormalities, Including Epigenetic Inhibition of Superoxide Dismutase 2, in Pulmonary Hypertension and Cancer: Therapeutic Implications.
Background.Single nucleotide polymorphisms (SNPs) of antioxidants, including superoxide dismutase 2 (SOD2) and glutathione peroxidase 1 (GPX1), play an important role in the risk for cancer and metabolic disorders.
Restricting MnSOD expression or inhibiting AMPK suppresses the metabolic switch and dampens the viability of transformed cells indicating that the MnSOD/AMPK axis is critical to support cancer cell bioenergetics.
The analysis included genetic polymorphisms in five redox related genes: GPX1 (rs1050450), GPX4 (rs713041), SOD2 (rs4880), SEPP1 (rs3877899) and SEP15 (rs5859), lipid peroxidation, the activities of antioxidant enzymes determined in blood compartments as well as plasma concentration of selenium - an antioxidant trace element involved in cancer.
Water pipe and cigarette smoking were more strongly associated with cancer risk among individuals with the TT genotype for SOD2 (OR [CI 95%] = 4.41 [1.86-10.42]) as compared with those with the CC genotype (OR [CI 95%] = 2.26 [0.97-6.74]).
Hazard ratios for 8 additional SNPs in CYP2E1, GPx2, SOD1, and SOD2, though not statistically significant, were suggestive of differences in allele hazards for all-cause and/or cancer death.
These two functional polymorphisms (Val-9Ala and Ile58Thr) in MnSOD gene did not associate with susceptibility risk of these cancer patients in Thailand.
In the past two decades, research has established that SOD2 transcriptional activity is controlled, at least in part, via epigenetic mechanisms at different stages in the development of human cancer.
The homozygous AA genotype of MnSODVal16Ala was significantly more prevalent in the cancer group than the control group (92 vs 13 per cent, respectively), while the heterozygous AV genotype of MnSODVal16Ala was more prevalent in the control group than the cancer group (87 vs 8 per cent, respectively) (p < 0.001).
Transgenic mice expressing a luciferase reporter gene under the control of the human MnSOD promoter demonstrate that the level of MnSOD is reduced prior to the formation of cancer.
This review presents recent evidence and emerging questions regarding the p53-MnSOD-p66shc connection, and discusses how dissection of a circuitry comprising a tumor suppressor, an antioxidant, and a molecule regulating cell survival and mammalian lifespan can provide a framework to address important aspects related to the intricate connection between metabolism, aging, and cancer.
Western blot study showed that the relative expressions of MnSOD protein in cancer lesion and in adjacent normal tissue were 0.384 ± 0.038 and 0.766 ± 0.041, respectively (P= 0.000).