Expanding roles of superoxide dismutases in cell regulation and cancer

Abstract

Reactive oxygen species (ROS) have important roles in normal physiology and diseases, particularly cancer. Under normal physiological conditions, they participate in redox reactions and serve as second messengers for regulatory functions. Owing to aberrant metabolism, cancer cells accumulate excessive ROS, thus requiring a robustly active antioxidant system to prevent cellular damage. Superoxide dismutases (SODs) are enzymes that catalyze the removal of superoxide free radicals. There are three distinct members of this metalloenzyme family in mammals: SOD1 (Cu/ZnSOD), SOD2 (MnSOD) and SOD3 (ecSOD). SODs are increasingly recognized for their regulatory functions in growth, metabolism and oxidative stress responses, which are also crucial for cancer development and survival. Growing evidence shows that SODs are also potentially useful anticancer drug targets. This review will focus on recent research of SODs in cellular regulation, with emphasis on their roles in cancer biology and therapy.

Mitochondrial dysregulation and glycolytic insufficiency functionally impair CD8 T cells infiltrating human renal cell carcinoma

“…SOD1 and -2 play roles to neutralize cytoplasmic and mitochondrial ROS, respectively (45). SOD1 levels were unchanged in ccRCC CD8 TIL (Supplemental Figure 7, A and B).…”

Protective Effects of Hydrogen Sulfide Against Cigarette Smoke Exposure-Induced Placental Oxidative Damage by Alleviating Redox Imbalance via Nrf2 Pathway in Rats

“…SOD1 is the major intracellular form of SOD, accounting for ~80% total SOD proteins. SOD2 is exclusively localized in the mitochondrial matrix, whereas SOD3 is the secreted form that is mainly associated with the extracellular matrix of different tissues [63]. Together, these SOD enzymes scavenge superoxide anion into molecular oxygen and hydrogen peroxide, then CAT and GPx reduce hydrogen peroxide, thus preventing production of highly toxic hydroxyl radical [64].…”

“…In mammals, there are three distinctive SODs, SOD1, SOD2 and the extracellular SOD (SOD3) [63]. SOD1 is the major intracellular form of SOD, accounting for ~80% total SOD proteins.…”

High Resolution Proteomic Analysis of the Cervical Cancer Cell Lines Secretome Documents Deregulation of Multiple Proteases

“…SOD1 (Cu/ZnSOD), SOD2 (MnSOD) and SOD3 (ecSOD). SOD1 is mostly cytoplasmic, SOD2 is mitochondrial, whereas SOD3 is secreted (51). SOD2 has a very interesting role in oncogenesis, since in some cases its upregulation acts as a protective mechanism, whereas in other cases its down-regulation contributes to the accumulation of reactive oxygen species (ROS), inhibiting cell death and favoring oncogenesis.…”

“…SOD2 has a very interesting role in oncogenesis, since in some cases its upregulation acts as a protective mechanism, whereas in other cases its down-regulation contributes to the accumulation of reactive oxygen species (ROS), inhibiting cell death and favoring oncogenesis. Also, SOD2 expression levels depend on the stage of oncogenesis, since reduced levels of SOD2 are observed in the initial stages, whereas increased levels are observed in the late stages and particularly in metastatic tumors (51). Our goal was to study the SOD2 expression pattern as a secreted protein.…”