“Double-Edged Sword” Effect of Reactive Oxygen Species (ROS) in Tumor Development and Carcinogenesis

Zhao, Wei; Zhuang, Ping; Chen, Yifan; Wu, Yan; Zhong, Ming-Chao; Lun, Yi

doi:10.33549/physiolres.935007

Cited by 8 publications

(3 citation statements)

References 106 publications

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“…It is widely known that ROS accumulation can cause cell and tissue damage, and that it can also play a regulatory role as a signaling molecule [ 47 ]. Oxidative stress is the core mechanism of diabetes [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

Circ_005077 accelerates myocardial lipotoxicity induced by high-fat diet via CyPA/p47PHOX mediated ferroptosis

Ni,

Duan,

Bao

et al. 2024

Cardiovasc Diabetol

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The long-term high-fat diet (HFD) can cause myocardial lipotoxicity, which is characterized pathologically by myocardial hypertrophy, fibrosis, and remodeling and clinically by cardiac dysfunction and heart failure in patients with obesity and diabetes. Circular RNAs (circRNAs), a novel class of noncoding RNA characterized by a ring formation through covalent bonds, play a critical role in various cardiovascular diseases. However, few studies have been conducted to investigate the role and mechanism of circRNA in myocardial lipotoxicity. Here, we found that circ_005077, formed by exon 2–4 of Crmp1, was significantly upregulated in the myocardium of an HFD-fed rat. Furthermore, we identified circ_005077 as a novel ferroptosis-related regulator that plays a role in palmitic acid (PA) and HFD-induced myocardial lipotoxicity in vitro and in vivo. Mechanically, circ_005077 interacted with Cyclophilin A (CyPA) and inhibited its degradation via the ubiquitination proteasome system (UBS), thus promoting the interaction between CyPA and p47phox to enhance the activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase responsible for ROS generation, subsequently inducing ferroptosis. Therefore, our results provide new insights into the mechanisms of myocardial lipotoxicity, potentially leading to the identification of a novel therapeutic target for the treatment of myocardial lipotoxicity in the future.

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Section: Discussionmentioning

confidence: 99%

Circ_005077 accelerates myocardial lipotoxicity induced by high-fat diet via CyPA/p47PHOX mediated ferroptosis

Ni,

Duan,

Bao

et al. 2024

Cardiovasc Diabetol

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“…Oxidative stress displays a "double-edged sword" effect on the occurrence and development of tumors. On the one hand, ROS can activate growth-promoting signals, enhance the proliferation and invasion of tumor cells, and cause damage to biomolecules; on the other hand, ROS can enhance antitumor signaling pathways by initiating oxidative stress-induced apoptosis and autophagy in cancer cells [8].…”

Section: Ros Rns and Antioxidants In Cancermentioning

confidence: 99%

Oxidative Stress and Redox-Dependent Pathways in Cholangiocarcinoma

Caligiuri,

Becatti,

Porro

et al. 2023

Antioxidants

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Cholangiocarcinoma (CCA) is a primary liver tumor that accounts for 2% of all cancer-related deaths worldwide yearly. It can arise from cholangiocytes of biliary tracts, peribiliary glands, and possibly from progenitor cells or even hepatocytes. CCA is characterized by high chemoresistance, aggressiveness, and poor prognosis. Potentially curative surgical therapy is restricted to a small number of patients with early-stage disease (up to 35%). Accumulating evidence indicates that CCA is an oxidative stress-driven carcinoma resulting from chronic inflammation. Oxidative stress, due to enhanced reactive oxygen species (ROS) production and/or decreased antioxidants, has been recently suggested as a key factor in cholangiocyte oncogenesis through gene expression alterations and molecular damage. However, due to different experimental models and conditions, contradictory results regarding oxidative stress in cholangiocarcinoma have been reported. The role of ROS and antioxidants in cancer is controversial due to their context-dependent ability to stimulate tumorigenesis and support cancer cell proliferation or promote cell death. On these bases, the present narrative review is focused on illustrating the role of oxidative stress in cholangiocarcinoma and the main ROS-driven intracellular pathways. Heterogeneous data about antioxidant effects on cancer development are also discussed.

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“…Carcinogenesis is a complex, multicomponent, and not fully understood process, in which oxidative metabolism plays a paradoxical role [10]. On the one hand, reactive oxygen species (ROS) are needed for cancer cell proliferation, metastasis, and chemoresistance.…”

Section: Introductionmentioning

confidence: 99%

Activity of NAD(P)H-Oxidoreductases in Ovarian Cancer

Fedorova,

Voznesensky,

Sosnova

et al. 2024

Biomedicines

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Reactive oxygen species (ROS) play an important and controversial role in carcinogenesis. Microsomal redox chains containing NADH- and NADPH-dependent oxidoreductases are among the main sites of intracellular ROS synthesis, but their role in the oxidative balance has not been fully studied. Here, we studied the activity of cytochrome b5 reductase (CYB5R) and cytochrome P450 reductase (CYPOR) in ovarian cancer tissues and cells isolated from peritoneal fluid, along with the antioxidant capacity of peritoneal fluid. We used the developed a chemiluminescence assay based on stimulation with NADH and NADPH, which reflects the activity of CYB5R and CYPOR, respectively. The activity of CYB5R and CYPOR was significantly higher in moderately and poorly differentiated ovarian adenocarcinomas compared with well-differentiated adenocarcinomas and cystadenomas. For the chemotherapy-resistant tumors, the activity of tissue CYB5R and CYPOR was lower compared to the non-resistant tumors. In the peritoneal fluid, the antioxidant capacity significantly increased in this series, benign tumors < well-differentiated < moderately and poorly differentiated adenocarcinomas, so the antioxidant excess was observed for moderately and poorly differentiated adenocarcinomas. The antioxidant capacity of peritoneal fluid and the activity of CYB5R and CYPOR of cells isolated from peritoneal fluid were characterized by a direct moderate correlation for moderately and poorly differentiated adenocarcinomas. These results indicate the significant role of NAD(P)H oxidoreductases and the antioxidant potential of peritoneal fluid in cancer biochemistry. The parameters studied are useful for diagnostics and prognostics. The developed assay can be used to analyze CYB5R and CYPOR activity in other tissues and cells.

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“Double-Edged Sword” Effect of Reactive Oxygen Species (ROS) in Tumor Development and Carcinogenesis

Cited by 8 publications

References 106 publications

Circ_005077 accelerates myocardial lipotoxicity induced by high-fat diet via CyPA/p47PHOX mediated ferroptosis

Circ_005077 accelerates myocardial lipotoxicity induced by high-fat diet via CyPA/p47PHOX mediated ferroptosis

Oxidative Stress and Redox-Dependent Pathways in Cholangiocarcinoma

Activity of NAD(P)H-Oxidoreductases in Ovarian Cancer

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