Epigenetic regulation of peroxiredoxins: Implications in the pathogenesis of cancer

Ow, Suet-Hui; Chua, Pei‐Jou; Bay, Boon‐Huat

doi:10.1177/1535370216669834

Cited by 12 publications

(8 citation statements)

References 89 publications

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“…Also, several clinical trials have suggested that antioxidants benefit cancer therapy (27). Among these, Prx protein family (Prx I-VI) has been reported to be aberrantly expressed in various tumors, implying an important role of Prxs in carcinogenesis (28). Prx V is an atypical 2-cys-Prx which is widely expressed in cellular compartments.…”

Section: Discussionmentioning

confidence: 99%

Peroxiredoxin V Inhibits Emodin-induced Gastric Cancer Cell Apoptosis via the ROS/Bcl2 Pathway

Jin

Sun

Liu

et al. 2019

In Vivo

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Background/Aim: Peroxiredoxin (Prx) protein family is aberrantly expressed in various cancers including gastric cancer. Among the six family members, Prx V has been known as an antioxidant enzyme which scavenges intracellular reactive oxygen species (ROS) and modulates cellular apoptosis. This study aimed at investigating the role of Prx V in apoptosis of gastric cancer cells. Materials and Methods: Stably constructed Prx V knockdown, over-expression and mock AGS cells (a human gastric adenocarcinoma cell line) were used to study the effect of Prx V on emodin-induced apoptosis by western blotting, cell viability, apoptosis and ROS detection assays. Results: Overexpression of Prx V significantly decreased emodin-induced cellular apoptosis and ROS levels compared to Mock and Prx V knockdown AGS cells. Also, overexpression of Prx V down-regulated the expression of proapoptotic proteins, Bad and cleaved PARP, and increased the expression of anti-apoptotic protein, Bcl2. Conclusion: Prx V suppresses AGS cell apoptosis via scavenging intracellular ROS and modulating apoptosis-related markers. Gastric cancer (GC) is one of the most common malignancies worldwide; unfortunately, the majority of GC patients is diagnosed at an advanced stage and die within 24 months after surgery because of recurrence and metastasis (1). The cure rate of gastric cancer is extremely low and the risk of treatment is large. It is well known that reactive oxygen species ROS levels are high in cancer cells compared to normal cells. ROS such as hydrogen peroxide, superoxide anions etc. are produced during mitochondria metabolism (2). Low levels of ROS can act as second messengers by participating in a variety of cellular physiological activities such as signal transduction, apoptosis, aging, proliferation and migration of cells. On the contrary, high levels of ROS have been recognized as driving factors in numerous diseases including cancer, aging, neurodegenerative disease, diabetes, cardiovascular disease, stroke, and asthma (3, 4), by inducing lipid, protein and DNA oxidation (5) thereby resulting in increased cellular apoptosis. On the other hand, there are cellular antioxidant mechanisms that clear excessive ROS (6, 7), such as superoxide dismutase (SOD), catalase (Cat), glutathione peroxidase (Gpx) and peroxiredoxin (Prxs). Prx V is a member of the Prxs family, which plays crucial roles in protecting cells from oxidative stress. Prxs are 1183 This article is freely accessible online.

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Section: Discussionmentioning

confidence: 99%

Peroxiredoxin V Inhibits Emodin-induced Gastric Cancer Cell Apoptosis via the ROS/Bcl2 Pathway

Jin

Sun

Liu

et al. 2019

In Vivo

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“…According to the cysteine residues present at the carboxyl and N-terminus, Prxs may be divided into three categories: 1-Cys Prx, typical 2-Cys Prx and atypical 2-Cys Prx. Prx II belongs to the typical 2-Cys Prx class (22,23). Prx II is involved in regulating cell proliferation, differentiation, apoptosis and signaling pathways, and they serve antioxidative defense roles by reducing and detoxifying various reactive oxygen species (ROS) that incorporate hydrogen peroxide (H 2 O 2 ).…”

Section: Discussionmentioning

confidence: 99%

Downregulation of peroxiredoxin II suppresses the proliferation and metastasis of gastric cancer cells

Niu

Liu

et al. 2018

Oncol Lett

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Peroxiredoxin (Prx) II is an imperative member of the superfamily of peroxidases. It serves an essential role in scavenging organic hydroperoxide and HO. It is involved in the development of various malignant tumors. In order to investigate the significance of Prx II expressions level in gastric cancer (GC), downregulation of Prx II was performed to investigate its role in the proliferation and migration of gastric adenocarcinoma cells. In GC cells and 45 GC specimens, the mRNA and protein expression levels of Prx II were determined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis, respectively. The Prx II expression profile in another 116 GC specimens was also detected with immunohistochemistry (IHC). The changes in the proliferation and migration of MKN45 and MGC-803 cells folllowing transfection with small interfering RNA (siRNA) were detected by cell counting kit (CCK)-8, western blot analysis, and Transwell migration and invasion assays. The results revealed that the expression of Prx II in GC tissues and GC cells were significantly upregulated compared with the normal control. There was a significant association between the expression level of Prx II and various factors, including tumor size, histological differentiation, the depth of invasion, the stage of tumor-node-metastasis (TNM) and lymph node metastasis in GC (P<0.05). Survival in patients with higher Prx II expression was significantly decreased compared with those with lower Prx II expression (P<0.01). Prx II, depth of invasion, lymph node metastasis and distant metastasis were identified as independent prognosis factors of GC (P<0.05). Knockdown of Prx II significantly suppressed the proliferation and the migration of GC cells. These experiments revealed that Prx II promotes the development of GC, affecting the survival of patients with GC.

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“…Recent studies have shown that peroxiredoxins contribute significantly to the promotion and progression of cancer. Members of the peroxiredoxin family are seemingly overexpressed in several tumor tissues ( 20 – 22 ), and they promote cell proliferation and tumorigenesis through epithelial–mesenchymal transition ( 23 , 24 ). Hyperoxidation of peroxiredoxins by hydrogen peroxide induces their inactivation, and the sulfiredoxin reductive action reactivates them.…”

Section: Circadian Disruption and Cancermentioning

confidence: 99%

Circadian and Metabolic Perspectives in the Role Played by NADPH in Cancer

Méndez

Dı́az-Muñoz

2018

Front. Endocrinol.

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Physiological activity in healthy conditions requires a coordinated interaction between the molecular circadian clock and the network of biochemical pathways. An important metabolic parameter in the interface between these two entities is the redox state. Among the redox coenzymes that regulate the fluxes of enzymatic reactions is the NADP+/NADPH pair. Indeed, the main biosynthetic pathways need NADPH to serve as an electron donor for cellular anabolic transformations. The existence of a metabolic circadian clock is well established, and it was first identified in mammalian red blood cells. The metabolic circadian clock is independent of transcriptional activity and is sustained by the enzymatic complex peroxiredoxin/thioredoxin/NADPH. This complex shows 24-h redox fluctuations metabolizing H2O2 in various tissues and species (fungi, insects, and mammals). Although this NADPH-sensitive metabolic clock is autonomous in erythrocytes that lack a nucleus, it functions in concert with the transcriptional circadian clock in other cell types to accomplish the task of timing cellular physiology. During carcinogenesis, circadian alterations influence cell cycle onset and promote tumoral growth. These alterations also deregulate cellular energetics through a process known as aerobic glycolysis, or the Warburg effect. The Warburg effect is a typical response of cancer cells in which the metabolism turns into glycolysis even in the presence of functional mitochondria. This alteration has been interpreted as a cellular strategy to increase biomass during cancer, and one of its main factors is the availability of NADPH. This minireview explores the potential role of NADPH as a circadian and cancer-promoting metabolite.

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Epigenetic regulation of peroxiredoxins: Implications in the pathogenesis of cancer

Cited by 12 publications

References 89 publications

Peroxiredoxin V Inhibits Emodin-induced Gastric Cancer Cell Apoptosis via the ROS/Bcl2 Pathway

Peroxiredoxin V Inhibits Emodin-induced Gastric Cancer Cell Apoptosis via the ROS/Bcl2 Pathway

Downregulation of peroxiredoxin II suppresses the proliferation and metastasis of gastric cancer cells

Circadian and Metabolic Perspectives in the Role Played by NADPH in Cancer

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