Inhibition of TrxR2 suppressed NSCLC cell proliferation, metabolism and induced cell apoptosis through decreasing antioxidant activity

Bu, Lina; Li, Wei; Zhou, Ming; Shi, Jie; Fang, Ping; Yang, Shifeng

doi:10.1016/j.lfs.2017.04.008

Cited by 20 publications

(14 citation statements)

References 22 publications

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“…The overexpression and hyperactivation of cytoplasmic TRXR (TRXR1) have been reported for various cancer types, such as brain cancer [142], breast cancer [143], HCC [144], lung cancer [144,145], oral [146,147], and tongue squamous cell carcinoma [148] (Table 2). Mitochondrial TRXR (TRXR2) was also found to be upregulated in tumor tissue [149]. Moreover, tumor cells overexpress TRX [143,148,[150][151][152][153] to cope with excessive ROS, and its expression is closely related to the pathological grade of the tumor [154][155][156][157][158].…”

Section: The Thioredoxin System and Thioredoxin-domain-containing Promentioning

confidence: 99%

The NRF2, Thioredoxin, and Glutathione System in Tumorigenesis and Anticancer Therapies

et al. 2020

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Cancer remains an elusive, highly complex disease and a global burden. Constant change by acquired mutations and metabolic reprogramming contribute to the high inter- and intratumor heterogeneity of malignant cells, their selective growth advantage, and their resistance to anticancer therapies. In the modern era of integrative biomedicine, realizing that a personalized approach could benefit therapy treatments and patients’ prognosis, we should focus on cancer-driving advantageous modifications. Namely, reactive oxygen species (ROS), known to act as regulators of cellular metabolism and growth, exhibit both negative and positive activities, as do antioxidants with potential anticancer effects. Such complexity of oxidative homeostasis is sometimes overseen in the case of studies evaluating the effects of potential anticancer antioxidants. While cancer cells often produce more ROS due to their increased growth-favoring demands, numerous conventional anticancer therapies exploit this feature to ensure selective cancer cell death triggered by excessive ROS levels, also causing serious side effects. The activation of the cellular NRF2 (nuclear factor erythroid 2 like 2) pathway and induction of cytoprotective genes accompanies an increase in ROS levels. A plethora of specific targets, including those involved in thioredoxin (TRX) and glutathione (GSH) systems, are activated by NRF2. In this paper, we briefly review preclinical research findings on the interrelated roles of the NRF2 pathway and TRX and GSH systems, with focus given to clinical findings and their relevance in carcinogenesis and anticancer treatments.

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Section: The Thioredoxin System and Thioredoxin-domain-containing Promentioning

confidence: 99%

The NRF2, Thioredoxin, and Glutathione System in Tumorigenesis and Anticancer Therapies

et al. 2020

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“…Member of the family of pyridine nucleotide-disulfide oxidoreductases, component of the antioxidant thioredoxin system HCC [108] OS [109] LC [110] Peroxiredoxin 3 (Prx3)…”

Section: Function Tumor Type Referencesmentioning

confidence: 99%

Modulation of Mitochondrial Metabolic Reprogramming and Oxidative Stress to Overcome Chemoresistance in Cancer

et al. 2020

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Metabolic reprogramming, carried out by cancer cells to rapidly adapt to stress such as hypoxia and limited nutrient conditions, is an emerging concepts in tumor biology, and is now recognized as one of the hallmarks of cancer. In contrast with conventional views, based on the classical Warburg effect, these metabolic alterations require fully functional mitochondria and finely-tuned regulations of their activity. In turn, the reciprocal regulation of the metabolic adaptations of cancer cells and the microenvironment critically influence disease progression and response to therapy. This is also realized through the function of specific stress-adaptive proteins, which are able to relieve oxidative stress, inhibit apoptosis, and facilitate the switch between metabolic pathways. Among these, the molecular chaperone tumor necrosis factor receptor associated protein 1 (TRAP1), the most abundant heat shock protein 90 (HSP90) family member in mitochondria, is particularly relevant because of its role as an oncogene or a tumor suppressor, depending on the metabolic features of the specific tumor. This review highlights the interplay between metabolic reprogramming and cancer progression, and the role of mitochondrial activity and oxidative stress in this setting, examining the possibility of targeting pathways of energy metabolism as a therapeutic strategy to overcome drug resistance, with particular emphasis on natural compounds and inhibitors of mitochondrial HSP90s.

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“…TXNRD2 encodes a mitochondrial TXNRD form, believed to be of importance in redox regulation in this cellular compartment [113]. Dysregulation of redox status is frequently observed in cancers, and TXNRD2 expression has been shown to be upregulated in some malignancies [114,115]. Because down-regulation of TXNRD2 in lung carcinoma cells induced apoptosis [115], and because TXNRD2 is a putative target of the WNT-signaling pathway [116], which is often deregulated in CRC, TXNRD2 may be acting as an oncogene in the context of tumor progression by modulating apoptosis signaling.…”

Section: Hallmark: Resisting Cell Deathmentioning

confidence: 99%

“…Interestingly, TXNRD1 expression was detectable in human colon cancer HT29 cells grown in monolayers, but not when grown as spheroids or as tumors in SCID mice, which may complicate comparative analyses across studies [121]. Mitochondrial TXNRD2, in addition to its potential role in other cancer-enabling characteristics, appears to promote cell proliferation, cell invasion and migration [115], which was shown primarily in mouse embryonic fibroblasts, where activation of hypoxia-inducible factor-1α signaling failed in absence of TXNRD2 [122]. TXNRD2 activity appears to be positively regulated by p53R2 [123].…”

Section: Hallmark: Cell Proliferation Cell Cycle Regulationmentioning

confidence: 99%

“…Unfortunately, other information regarding TXNRD1’s role in metastasis is limited to tissues outside the intestinal tract (reviewed in [37]), including targeted downregulation of TXNRD1 in mouse lung carcinoma cells that had similarly resulted in the reversal in the morphology and anchorage-independent growth properties [131]. The mitochondrial TXNRD2 also appears to promote cell invasion and migration [115], which was shown in mouse embryonic fibroblasts, where activation of hypoxia-inducible factor-1α signaling failed in the absence of TXNRD2 [122]. TXNRD2 activity appears to be positively regulated by p53R2 [123].…”

Section: Hallmark: Metastatic Ability (Activating Invasion and Metastmentioning

confidence: 99%

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Selenoproteins in colon cancer

Peters

Carlson

Gladyshev

et al. 2018

Free Radical Biology and Medicine

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Selenocysteine-containing proteins (selenoproteins) have been implicated in the regulation of various cell signaling pathways, many of which are linked to colorectal malignancies. In this in-depth excurse into the selenoprotein literature, we review possible roles for human selenoproteins in colorectal cancer, focusing on the typical hallmarks of cancer cells and their tumor-enabling characteristics. Human genome studies of single nucleotide polymorphisms in various genes coding for selenoproteins have revealed potential involvement of glutathione peroxidases, thioredoxin reductases, and other proteins. Cell culture studies with targeted down-regulation of selenoproteins and studies utilizing knockout/transgenic animal models have helped elucidate the potential roles of individual selenoproteins in this malignancy. Those selenoproteins, for which strong links to development or progression of colorectal cancer have been described, may be potential future targets for clinical interventions.

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Inhibition of TrxR2 suppressed NSCLC cell proliferation, metabolism and induced cell apoptosis through decreasing antioxidant activity

Cited by 20 publications

References 22 publications

The NRF2, Thioredoxin, and Glutathione System in Tumorigenesis and Anticancer Therapies

The NRF2, Thioredoxin, and Glutathione System in Tumorigenesis and Anticancer Therapies

Modulation of Mitochondrial Metabolic Reprogramming and Oxidative Stress to Overcome Chemoresistance in Cancer

Selenoproteins in colon cancer

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