The effect of superoxide anion and hydrogen peroxide imbalance on prostate cancer: an integrative in vivo and in vitro analysis

Berto, Maiquidieli Dal; Bica, Cláudia Giuliano; Sá, Gustavo; Barbisan, Fernanda; Azzolin, Verônica Farina; Rogalski, Felipe; Cruz, Ivana Beatrice Mânica da

doi:10.1007/s12032-015-0700-1

Cited by 13 publications

(11 citation statements)

References 31 publications

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“…This variant has also been shown to be associated with a higher risk of pancreatic and non-small-cell lung carcinoma [ 62 , 72 ]. Contrary to this, other studies have demonstrated that the wild-type alanine phenotype carries a greater risk of prostrate, ovarian and breast cancer, suggesting a pro-tumorigenic role for fully-functional SOD2 in these cancers [ 144 , 145 , 146 ]. Other mechanisms that could influence mis-compartmentalization of SOD2, but that have been largely unexplored in cancer, are abnormal cleavage of target sequences due to changes in mitochondrial MPP expression, protein mis-folding or the existence of dysfunctional mitochondria and mitochondrial protein import machinery, which can occur due to redox stress [ 147 ].…”

Section: Post-translational Regulation Of Sod2mentioning

confidence: 91%

Insights into the Dichotomous Regulation of SOD2 in Cancer

et al. 2017

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While loss of antioxidant expression and the resultant oxidant-dependent damage to cellular macromolecules is key to tumorigenesis, it has become evident that effective oxidant scavenging is conversely necessary for successful metastatic spread. This dichotomous role of antioxidant enzymes in cancer highlights their context-dependent regulation during different stages of tumor development. A prominent example of an antioxidant enzyme with such a dichotomous role and regulation is the mitochondria-localized manganese superoxide dismutase SOD2 (MnSOD). SOD2 has both tumor suppressive and promoting functions, which are primarily related to its role as a mitochondrial superoxide scavenger and H2O2 regulator. However, unlike true tumor suppressor- or onco-genes, the SOD2 gene is not frequently lost, or rarely mutated or amplified in cancer. This allows SOD2 to be either repressed or activated contingent on context-dependent stimuli, leading to its dichotomous function in cancer. Here, we describe some of the mechanisms that underlie SOD2 regulation in tumor cells. While much is known about the transcriptional regulation of the SOD2 gene, including downregulation by epigenetics and activation by stress response transcription factors, further research is required to understand the post-translational modifications that regulate SOD2 activity in cancer cells. Moreover, future work examining the spatio-temporal nature of SOD2 regulation in the context of changing tumor microenvironments is necessary to allows us to better design oxidant- or antioxidant-based therapeutic strategies that target the adaptable antioxidant repertoire of tumor cells.

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Section: Post-translational Regulation Of Sod2mentioning

confidence: 91%

Insights into the Dichotomous Regulation of SOD2 in Cancer

et al. 2017

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“…Although cancer cells become adapted to increased ROS levels, the aberrant supraphysiological levels of either O 2 •− or H 2 O 2 markedly influence cell survival by reducing cell cycling and cell proliferation. Therefore, increased ROS levels are frequently used as cytotoxins in cancer patients (13, 23).…”

Section: Introductionmentioning

confidence: 99%

Carcinogenesis and Reactive Oxygen Species Signaling: Interaction of the NADPH Oxidase NOX1–5 and Superoxide Dismutase 1–3 Signal Transduction Pathways

Parascandolo

Laukkanen

2019

Antioxidants & Redox Signaling

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“…Low levels of hydrogen peroxide leads to caspase dependent cell death, while, high levels of hydrogen peroxide can activate caspase independent apoptosis as well as necrotic cell death [ 33 ]. MnPs were proposed as therapeutic molecules against cancer cells because they can lower superoxide levels and potentially increase the hydrogen peroxide levels in cancer cells [ 32 , 34 ]. We found that in combination with radiation, MnTE-2-PyP or MnTnBuOE-2-PyP increases hydrogen peroxide levels in the PC3 cells [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

The Addition of Manganese Porphyrins during Radiation Inhibits Prostate Cancer Growth and Simultaneously Protects Normal Prostate Tissue from Radiation Damage

et al. 2018

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Radiation therapy is commonly used for prostate cancer treatment; however, normal tissues can be damaged from the reactive oxygen species (ROS) produced by radiation. In separate reports, we and others have shown that manganese porphyrins (MnPs), ROS scavengers, protect normal cells from radiation-induced damage but inhibit prostate cancer cell growth. However, there have been no studies demonstrating that MnPs protect normal tissues, while inhibiting tumor growth in the same model. LNCaP or PC3 cells were orthotopically implanted into athymic mice and treated with radiation (2 Gy, for 5 consecutive days) in the presence or absence of MnPs. With radiation, MnPs enhanced overall life expectancy and significantly decreased the average tumor volume, as compared to the radiated alone group. MnPs enhanced lipid oxidation in tumor cells but reduced oxidative damage to normal prostate tissue adjacent to the prostate tumor in combination with radiation. Mechanistically, MnPs behave as pro-oxidants or antioxidants depending on the level of oxidative stress inside the treated cell. We found that MnPs act as pro-oxidants in prostate cancer cells, while in normal cells and tissues the MnPs act as antioxidants. For the first time, in the same in vivo model, this study reveals that MnPs enhance the tumoricidal effect of radiation and reduce oxidative damage to normal prostate tissue adjacent to the prostate tumor in the presence of radiation. This study suggests that MnPs are effective radio-protectors for radiation-mediated prostate cancer treatment.

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The effect of superoxide anion and hydrogen peroxide imbalance on prostate cancer: an integrative in vivo and in vitro analysis

Cited by 13 publications

References 31 publications

Insights into the Dichotomous Regulation of SOD2 in Cancer

Insights into the Dichotomous Regulation of SOD2 in Cancer

Carcinogenesis and Reactive Oxygen Species Signaling: Interaction of the NADPH Oxidase NOX1–5 and Superoxide Dismutase 1–3 Signal Transduction Pathways

The Addition of Manganese Porphyrins during Radiation Inhibits Prostate Cancer Growth and Simultaneously Protects Normal Prostate Tissue from Radiation Damage

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