Redox Homeostasis and Cellular Antioxidant Systems: Crucial Players in Cancer Growth and Therapy

Marengo, Barbara; Nitti, Mariapaola; Furfaro, Anna Lisa; Colla, Renata; Ciucis, Chiara De; Marinari, Umberto M.; Pronzato, Maria Adelaide; Traverso, Nicola; Domenicotti, Cinzia

doi:10.1155/2016/6235641

Cited by 250 publications

(195 citation statements)

References 222 publications

(188 reference statements)

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“…Intracellular redox homeostasis is regulated by a balance between ROS generation and elimination (Chio and Tuveson, 2017; Marengo et al, 2016). Abnormal ROS accumulation could be due to increased ROS production and/or reduced presence of antioxidants.…”

Section: Discussionmentioning

confidence: 99%

Alteration of Tumor Metabolism by CD4+ T Cells Leads to TNF-α-Dependent Intensification of Oxidative Stress and Tumor Cell Death

Habtetsion

Ding

et al. 2018

Cell Metabolism

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SUMMARY The inhibitory effects of cancer on T cell metabolism have been well established, but the metabolic impact of immunotherapy on tumor cells is poorly understood. Here, we developed a CD4+ T cell-based adoptive immunotherapy protocol that was curative for mice with implanted colorectal tumors. By conducting metabolic profiling on tumors, we show that adoptive immunotherapy profoundly altered tumor metabolism, resulting in glutathione depletion and accumulation of reactive oxygen species (ROS) in tumor cells. We further demonstrate that T cell-derived tumor necrosis factor alpha (TNF-α) can synergize with chemotherapy to intensify oxidative stress and tumor cell death in an NADPH (nicotinamide adenine dinucleotide phosphate hydrogen) oxidase-dependent manner. Reduction of oxidative stress, by preventing TNF-α-signaling in tumor cells or scavenging ROS, antagonized the therapeutic effects of adoptive immunotherapy. Conversely, provision of pro-oxidants after chemotherapy can partially recapitulate the antitumor effects of T cell transfer. These findings imply that reinforcing tumor oxidative stress represents an important mechanism underlying the efficacy of adoptive immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Alteration of Tumor Metabolism by CD4+ T Cells Leads to TNF-α-Dependent Intensification of Oxidative Stress and Tumor Cell Death

Habtetsion

Ding

et al. 2018

Cell Metabolism

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“…Balance of cellular H 2 O 2 is decisive for cell fate: low and intermediate levels of H 2 O 2 stimulate loss of cell homeostasis and increased adaptation to stress which leads to neoplastic transformation while high levels of H 2 O 2 induce cell death [4]. In order to test the correlation between miR-29b and ROS in EOC cells, here we evaluated the expression of miR-29b in both EOC cell lines treated with H 2 O 2 for different periods of time.…”

Section: Resultsmentioning

confidence: 99%

“…Reactive oxygen species (ROS) are a series of highly reactive molecules principally derived from the oxygen that is consumed in various metabolic activities occurring mainly in the mitochondria, peroxisomes, and the endoplasmic reticulum [4]. Regulation of intracellular ROS is critical for cellular homeostasis, since different ROS levels could lead to different biological responses.ROS at low and moderate levels acts as signaling molecules that sustain cellular proliferation, differentiation, and cell cycle progression as well as activate stress responsive survival pathways [5].…”

Section: Introductionmentioning

confidence: 99%

Mir-29b Regulates Oxidative Stress by Targeting SIRT1 in Ovarian Cancer Cells

Hou

Zuo

et al. 2017

Cell Physiol Biochem

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Background: Metabolic abnormalities are frequently observed in multiple malignancies including epithelial ovarian cancer (EOC), among which imbalance between generation and elimination of reactive oxygen species (ROS) plays a critical role in EOC onset and progression. Here we investigated the role of miR-29b, a well-established tumor-suppressor miRNA in metabolic regulation of EOC cells. Methods: cell viability and apoptosis in miR-29b inhibited and over-expressed EOC cells were evaluated by CCK8 and Annexin V–FITC/PI assays. Change in miR-29b was detected in EOC cells incubated in H₂O₂ culture by q-PCR. Relative ROS levels were also detected in different EOC cultures, including modified miR-29b and SIRT1 levels as well as H₂O₂ incubation. A luciferase reporter assay was employed to detect the direct binding of miR-29b to SIRT1 3’ UTR. Changes in cell viability and ROS levels were assessed in SIRT1-knocked down EOC cells. Results: miR-29b expression correlates with decreased EOC cell viability and increased apoptosis. H₂O₂ downregulated miR-29b in a time and dose-dependent manner. miR-29b expression negatively correlated with ROS levels, whereas SIRT1 significantly stimulated ROS formation. Luciferase reporter assays confirmed miR-29b downregulation of SIRT1by directly targeting its mRNA 3’-UTR. SIRT1 silencing rescues cell viability of H₂O₂ treated cells. Also, SIRT1 inhibition blocked cell apoptosis induced by H₂O₂ as well as reduced intracellular ROS levels. Conclusion: Together, our findings indicated that the miR-29b/SIRT1 axis has a protective effect against H₂O₂-induced damage of cell viability and oxidative stress and may provide novel options for miR-29b-based therapeutic approaches for EOC treatment.

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“…HO-1 expression levels in normal tissues not directly involved in hemoglobin metabolism are low, but HO-1 exists in almost all tissues [13]. In addition, HO-1 is involved in the maintenance of cell homeostasis, plays a central role in adaptation to cellular stress, protects and prolongs cell survival, and inhibits carcinogenesis [11,14,15]. However, in many cancer tissues, HO-1 is induced, synthesized, and expressed as a result of various stresses such as hypoxia [16], and its expression is higher than in surrounding normal tissues [17,18].…”

Section: Introductionmentioning

confidence: 99%

Increasing Heme Oxygenase-1-Expressing Macrophages Indicates a Tendency of Poor Prognosis in Advanced Colorectal Cancer

Kimura¹,

Aung²,

Ohe³

et al. 2019

Digestion

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Background: Many cancers express heme oxygenase-1 (HO-1) at a higher frequency than healthy tissues, and this elevated expression is associated with cancer prognosis. Here, we aim to clarify the correlation between HO-1-expressing macrophage numbers and clinicopathological parameters of advanced colorectal cancer. Materials and Methods: Formalin-fixed and paraffin-embedded tissues of patients with advanced colorectal cancer were used. To detect HO-1 expression in macrophages, immunohistochemistry was performed. The number of positive cells was measured. Furthermore, HO-1 mRNA in colorectal cancer was examined by reverse transcription polymerase chain reaction. Results: Among the HO-1-negative and HO-1-positive groups, 58.02 and 85.00% of cases, respectively, were positive for lymph node metastasis. The disease-free survival (DFS) time was significantly shorter (p < 0.05) in the HO-1-positive group (2.44 years) than in the HO-1-negative group (4.09 years). However, according to the Cox proportional-hazards regression model, the HO-1-positive group could not be a risk factor of poor prognosis. HO-1 mRNA expression was confirmed in colorectal normal and cancer tissues. Conclusion: In this study, the correlation between HO-1-expressing macrophages and clinicopathological parameters in the tumor microenvironment of colorectal cancer was studied for the first time, and the expression was associated with lymph node metastasis and shortening of DFS.

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Redox Homeostasis and Cellular Antioxidant Systems: Crucial Players in Cancer Growth and Therapy

Cited by 250 publications

References 222 publications

Alteration of Tumor Metabolism by CD4+ T Cells Leads to TNF-α-Dependent Intensification of Oxidative Stress and Tumor Cell Death

Alteration of Tumor Metabolism by CD4+ T Cells Leads to TNF-α-Dependent Intensification of Oxidative Stress and Tumor Cell Death

Mir-29b Regulates Oxidative Stress by Targeting SIRT1 in Ovarian Cancer Cells

Increasing Heme Oxygenase-1-Expressing Macrophages Indicates a Tendency of Poor Prognosis in Advanced Colorectal Cancer

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