The functional role of peroxiredoxin 3 in reactive oxygen species, apoptosis, and chemoresistance of cancer cells

Li, Lianqin; Yu, Ai-Qun

doi:10.1007/s00432-015-1916-3

Cited by 27 publications

(21 citation statements)

References 85 publications

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“…Table 2), and included a number of heat stress proteins and chaperones, which are normally induced in response to the accumulation of unfolded proteins formed under different stress conditions (62). Overall, it seems that Prx3 plays a defining role in mitochondrial functioning, and this notion is supported by studies conducted in mammals (63,64). Nevertheless, there is a considerable degree of redundancy with Prx5, based on the overlap of gene expression patterns of the single mutants and the additive nature of transcript levels in the DM (Fig.…”

Section: Discussionmentioning

confidence: 68%

Mitochondrial peroxiredoxins are essential in regulating the relationship between Drosophila immunity and aging

Odnokoz

Nakatsuka

Klichko

et al. 2017

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Previously, we have shown that flies under-expressing the two mitochondrial peroxiredoxins (Prxs), dPrx3 and dPrx5, display increases in tissue-specific apoptosis and dramatically shortened life span, associated with a redox crisis, manifested as changes in GSH:GSSG and accumulation of protein mixed disulfides. To identify specific pathways responsible for the observed biological effects, we performed a transcriptome analysis. Functional clustering revealed a prominent group enriched for immunity-related genes, including a considerable number of NF-kB-dependent antimicrobial peptides (AMP) that are up-regulated in the Prx double mutant. Using qRT-PCR analysis we determined that the age-dependent changes in AMP levels in mutant flies were similar to those observed in controls when scaled to percentage of life span. To further clarify the role of Prx-dependent mitochondrial signaling, we expressed different forms of dPrx5, which unlike the uniquely mitochondrial dPrx3 is found in multiple subcellular compartments, including mitochondrion, nucleus and cytosol. Ectopic expression of dPrx5 in mitochondria but not nucleus or cytosol partially extended longevity under normal or oxidative stress conditions while complete restoration of life span occurred when all three forms of dPrx5 were expressed from the wild type dPrx5 transgene. When dPrx5 was expressed in mitochondria or in all three compartments, it substantially delayed the development of hyperactive immunity while expression of cytosolic or nuclear forms had no effect on the immune phenotype. The data suggest a critical role of mitochondria in development of chronic activation of the immune response triggered by impaired redox control.

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Section: Discussionmentioning

confidence: 68%

Mitochondrial peroxiredoxins are essential in regulating the relationship between Drosophila immunity and aging

Odnokoz

Nakatsuka

Klichko

et al. 2017

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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“…PRDX3 controls the apoptotic signaling pathway through the regulation of cytochrome c release from the mitochondria, as well as through interaction with the complex of leucine zipper-bearing kinase (LZK) and IKB kinase (IKK). Therefore, it is conceivable that drugs targeting PRDX3 and the mitochondrion-specific electron suppliers, Trx2, TrxR2 and Srx, could represent a good strategy for improving the response to various chemotherapeutic agents, including cisplatin, paclitaxel and etoposide (162,163). Finally, there is evidence that PRDX5 is also involved in the chemoresistance to adriamycin, bleomycin, vinblastine and dacarbazine in patients affected with aggressive Hodgkin's lymphomas (127) and in vitro in the lung carcinoma U1810 cell line (164), always by inhibiting chemotherapeutic-induced apoptosis.…”

Section: Prdxs and Chemoresistancementioning

confidence: 99%

The role of peroxiredoxins in cancer

Nicolussi

D’Inzeo

Capalbo

et al. 2017

Molecular and Clinical Oncology

154

126

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Peroxiredoxins (PRDXs) are a ubiquitously expressed family of small (22–27 kDa) non-seleno peroxidases that catalyze the peroxide reduction of H2O2, organic hydroperoxides and peroxynitrite. They are highly involved in the control of various physiological functions, including cell growth, differentiation, apoptosis, embryonic development, lipid metabolism, the immune response, as well as cellular homeostasis. Although the protective role of PRDXs in cardiovascular and neurological diseases is well established, their role in cancer remains controversial. Increasing evidence suggests the involvement of PRDXs in carcinogenesis and in the development of drug resistance. Numerous types of cancer cells, in fact, are characterized by an increase in reactive oxygen species (ROS) production, and often exhibit an altered redox environment compared with normal cells. The present review focuses on the complex association between oxidant balance and cancer, and it provides a brief account of the involvement of PRDXs in tumorigenesis and in the development of chemoresistance.

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“…For instance, mitochondria rely on superoxide dismutase 2, peroxiredoxin 3, thioredoxin 2, and thioredoxin reductase 2 for antioxidant defense and signaling transduction, but they do not rely on catalase (Rabilloud et al, 2001; Jones, 2006). Considering the crucial role that mitochondrial-generated ROS have in cancer initiation, progression, and apoptosis, the targeting of key antioxidant and redox signaling transduction systems in this compartment (e.g., PRDX3 Li and Yu, 2015) may have important consequences for global cell metabolism. However, it should be noted that targeting these antioxidants may lead to compensatory responses by the other antioxidants.…”

Section: Role Of Antioxidant Defenses In Cancermentioning

confidence: 99%

New Challenges to Study Heterogeneity in Cancer Redox Metabolism

Benfeitas

Uhlén

Nielsen

et al. 2017

Front. Cell Dev. Biol.

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Reactive oxygen species (ROS) are important pathophysiological molecules involved in vital cellular processes. They are extremely harmful at high concentrations because they promote the generation of radicals and the oxidation of lipids, proteins, and nucleic acids, which can result in apoptosis. An imbalance of ROS and a disturbance of redox homeostasis are now recognized as a hallmark of complex diseases. Considering that ROS levels are significantly increased in cancer cells due to mitochondrial dysfunction, ROS metabolism has been targeted for the development of efficient treatment strategies, and antioxidants are used as potential chemotherapeutic drugs. However, initial ROS-focused clinical trials in which antioxidants were supplemented to patients provided inconsistent results, i.e., improved treatment or increased malignancy. These different outcomes may result from the highly heterogeneous redox responses of tumors in different patients. Hence, population-based treatment strategies are unsuitable and patient-tailored therapeutic approaches are required for the effective treatment of patients. Moreover, due to the crosstalk between ROS, reducing equivalents [e.g., NAD(P)H] and central metabolism, which is heterogeneous in cancer, finding the best therapeutic target requires the consideration of system-wide approaches that are capable of capturing the complex alterations observed in all of the associated pathways. Systems biology and engineering approaches may be employed to overcome these challenges, together with tools developed in personalized medicine. However, ROS- and redox-based therapies have yet to be addressed by these methodologies in the context of disease treatment. Here, we review the role of ROS and their coupled redox partners in tumorigenesis. Specifically, we highlight some of the challenges in understanding the role of hydrogen peroxide (H2O2), one of the most important ROS in pathophysiology in the progression of cancer. We also discuss its interplay with antioxidant defenses, such as the coupled peroxiredoxin/thioredoxin and glutathione/glutathione peroxidase systems, and its reducing equivalent metabolism. Finally, we highlight the need for system-level and patient-tailored approaches to clarify the roles of these systems and identify therapeutic targets through the use of the tools developed in personalized medicine.

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The functional role of peroxiredoxin 3 in reactive oxygen species, apoptosis, and chemoresistance of cancer cells

Abstract: Since most of chemotherapy or radiotherapy for cancers is through ROS increase and apoptotic induction, PRX3 might be involved in the chemotherapeutic resistance of cancers.

Cited by 27 publications

References 85 publications

Mitochondrial peroxiredoxins are essential in regulating the relationship between Drosophila immunity and aging

Mitochondrial peroxiredoxins are essential in regulating the relationship between Drosophila immunity and aging

The role of peroxiredoxins in cancer

New Challenges to Study Heterogeneity in Cancer Redox Metabolism

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