Expression of peroxiredoxin and thioredoxin in human lung cancer and paired normal lung

Park, Joo Hun; Kim, Young Sun; Lee, Hye Lim; Shim, Jin Young; Lee, Keu Sung; Oh, Yoon Sin; Shin, Sungwon; Choi, Young Hwa; Park, Kwang Joo; Park, Rae Woong; Hwang, Sung Chul

doi:10.1111/j.1440-1843.2006.00849.x

Cited by 93 publications

(75 citation statements)

References 27 publications

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“…In contrast, we found a reduced expression of peroxiredoxin 6 as a result of auranofin treatment. Peroxiredoxins are increased in a number of cancers, including lung cancer [53], and have been correlated to radioresistance and resistance to cisplatin [54] The peroxiredoxins also influence a variety of cellular processes that are sensitive to reactive oxygen species and play a role in signal transduction and gene expression related to alteration in cellular reactive oxygen species levels [55]. In many cases increased peroxiredoxin expression correlated to chemoresistance; our results suggest that treatment with both drugs, modifying the expression of peroxiredoxin, disrupts total cellular redox homeostasis and induces apoptosis.…”

Section: Functional Roles Of the Identified Proteinsmentioning

confidence: 99%

Exploring the biochemical mechanisms of cytotoxic gold compounds: a proteomic study

et al. 2010

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We have recently shown that a group of structurally diverse gold compounds are highly cytotoxic toward a panel of 36 human tumor cell lines through a variety of biochemical mechanisms. A classic proteomic approach is exploited here to gain deeper insight into those mechanisms. This investigation is focused on Auoxo6, a novel binuclear gold(III) complex, and auranofin, a clinically established gold(I) antiarthritic drug. First, the 72-h cytotoxicity profiles of Auoxo6 and auranofin were determined against A2780 human ovarian carcinoma cells. Subsequently, protein extraction from gold-treated A2780 cells sensitive to cisplatin and 2D gel electrophoresis separation were carried out according to established procedures. Notably, both metallodrugs caused relatively modest changes in protein expression in comparison with controls as only 11 out of approximately 1,300 monitored spots showed appreciable quantitative changes. Very remarkably, six altered proteins were in common between the two treatments. Eight altered proteins were identified by mass spectrometry; among them was ezrin, a protein associated with the cytoskeleton and involved in apoptosis. Interestingly, two altered proteins, i.e., peroxiredoxins 1 and 6, are known to play crucial roles in the cell redox metabolism. Increased cleavage of heterogeneous ribonucleoprotein H was also evidenced, consistent with caspase 3 activation. Overall, the results of the present proteomic study point out that the mode of action of Auoxo6 is strictly related to that of auranofin, that the induced changes in protein expression are limited and selective, that both gold compounds trigger caspase 3 activation and apoptosis, and that a few affected proteins are primarily involved in cell redox homeostasis.

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Section: Functional Roles Of the Identified Proteinsmentioning

confidence: 99%

Exploring the biochemical mechanisms of cytotoxic gold compounds: a proteomic study

et al. 2010

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“…Specifically, increased PRX expression has been reported in several studies of both lung cancer and breast cancer (Noh et al 2001;Park et al 2006). With respect to human lung cancer, differential PRX expression was reported for various tumor subtypes, including adenocarcinoma and high-grade squamous cell carcinoma, as well as advanced tumor stages (Chen et al 2006).…”

Section: Links Between Chemotherapy Resistance and Prx Activitymentioning

confidence: 99%

“…With respect to human lung cancer, differential PRX expression was reported for various tumor subtypes, including adenocarcinoma and high-grade squamous cell carcinoma, as well as advanced tumor stages (Chen et al 2006). Interestingly, modified (presumably oxidized) PrdxI accumulates in human lung cancer samples (Park et al 2006), indicating, perhaps, a role for the chaperone function of PrdxI in tumorigenesis (or elevated peroxide signaling). Furthermore, a recent study reported that increased Srx expression deregulates PrdxIV activity in lung cancers, and Srx and PrdxIV were found to be required for several key aspects of tumor growth and metastasis; e.g., anchorage-dependent colony formation, cell migration, and invasion (Wei et al 2011).…”

Section: Links Between Chemotherapy Resistance and Prx Activitymentioning

confidence: 99%

“…Similar to Prxs, both Trx and Trx reductase (Trr) levels are increased in several human cancers Park et al 2006), and overproduction of Trx in MCF-7 human breast cancer cells induced tumorigenesis in a manner dependent on the catalytic cysteines . A detailed description of the roles of the Trxs in tumorigenesis is beyond the scope of this review, but it should be noted that increased Trx levels contribute to many of the hallmarks of cancer, including increased proliferation, resistance to apoptosis, and increased angiogenesis (Powis and Kirkpatrick 2007).…”

Section: Links Between Chemotherapy Resistance and Prx Activitymentioning

confidence: 99%

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Peroxiredoxins, gerontogenes linking aging to genome instability and cancer

2012

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Age is the highest risk factor known for a large number of maladies, including cancers. However, it is unclear how aging mechanistically predisposes the organism to such diseases and which gene products are the primary targets of the aging process. Recent studies suggest that peroxiredoxins, antioxidant enzymes preventing tumor development, are targets of age-related deterioration and that bolstering their activity (e.g., by caloric restriction) extends cellular life span. This review focuses on how the peroxiredoxin functions (i.e., as peroxidases, signal transducers, and molecular chaperones) fit with contemporary theories of aging and whether peroxiredoxins could be targeted therapeutically in the treatment of age-associated cancers.

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“…From these reports and our former study, Prdx1 appears to have a possible correlation with an anti-tumor effect by producing epigenetic changes in cancer patients. On the other hand, some researchers have mentioned that this protein may be involved with cell proliferation and tumor growth in several kinds of solid cancers (11)(12)(13)(14)(15).In order to contribute to the controversial discussion about the influence of Prdx1 expression in malignant tumors, we examined the expression of this protein in 114 cases of ESCC by immunohistochemistry and evaluated the correlations with the clinical parameters of ESCC to determine whether or not the expression of PrdxI in ESCC plays an important role in tumor progression. ONCOLOGY REPORTS 18: 867-871, 2007 867 Tumor suppressor Prdx1 is a prognostic factor in esophageal squamous cell carcinoma patients ISAMU HOSHINO, HISAHIRO MATSUBARA, YASUNORI AKUTSU, TAKANORI NISHIMORI, YASUO YONEYAMA, KENTARO MURAKAMI, HARUHITO SAKATA, KAZUYUKI MATSUSHITA and TAKENORI OCHIAI…”

mentioning

confidence: 99%

Tumor suppressor Prdx1 is a prognostic factor in esophageal squamous cell carcinoma patients

Hoshino¹,

Matsubara²,

Akutsu³

et al. 2007

Oncol Rep

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Abstract. Peroxiredoxins (Prdxs) are a family of antioxidant enzymes that are also known as scavengers of peroxide in mammalian cells. Some reports have shown that the overexpression of Prdx1, which is one of the peroxiredoxins that is a ubiquitously expressed protein, was related to a poor prognosis in several types of human cancers. In this study, we investigated the expression levels of Prdx1 in esophageal squamous cell carcinoma by immunohistochemistry, and the correlation between the Prdx1 expression and the clinical status was elucidated. Immunohistochemical staining was performed in 114 samples which were collected from surgical esophageal cancer specimens. Cytoplasmic staining of Prdx1 was evaluated based on the following scoring criteria: Grade I, negative or weak staining; Grade II, moderate staining; and Grade III, strong staining. The percentage of patients with a Grade I expression of Prx1 was 20% (23 of 114), 44% had Grade II (50 of 114), and 36% had Grade III (41 of 114). The Prdx1 immunoreactivity showed an inverse significant correlation with T-category (P<0.0001), lymph node metastasis (P=0.048), and stage (P=0.001). In addition, the patients with tumors exhibiting a reduced Prdx1 expression had shorter overall survival (P=0.022) in comparison to the patients with tumors which had a higher Prdx1 expression. Currently, Prdx1 has been shown to act as a tumor suppressor. Our results provide strong evidence that the reduced Prdx1 expression is an important factor in esophageal squamous cancer progression and could serve as a useful prognostic marker. IntroductionEsophageal cancer is the eighth most frequent cancer and the sixth most frequent cause of death from malignant disease in the world (1). Esophageal squamous cell carcinoma (ESCC) is the most common type in Japan (2). A large number of reports about genetic changes in ESCC have already been published, but little is known about the major tumor suppressor genes or major oncogenes in the process of tumor progression of this malignant disease. ESCC is still a fatal malignancy with a 5-year rate of 5% to 20% for advanced stage patients undergoing a curative resection (3). This miserable prognosis for ESCC involves not only the aggressive character of this tumor but also the limited number of useful markers available for diagnostic purposes.Therefore, better markers which indicate the malignant potential of ESCC should help in the prognosis or optimal treatment of the patients suffering from this disease. In this study, we focus on Prdx1, one of the peroxiredoxins (Prdxs) belonging to a novel antioxidant family, which has been reported to be a tumor suppressor gene. Prdx1 has been thought to have an inhibitory function for both c-Abl and c-Myc, of which active forms cause several neoplasms (4,5). Neumann et al (6) showed, using Prdx1 knockout mice, that Prdx1 expression correlated with the reactive oxygen species and the incidence of malignant disease. Moreover, our previous study using a cDNA microarray showed that one of the novel histone deacet...

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Expression of peroxiredoxin and thioredoxin in human lung cancer and paired normal lung

Abstract: The upregulation of Prx I, Prx III and thioredoxin in lung cancer tissue may represent an attempt by tumour cells to adjust to the microenvironment in a manner that is advantageous to survival and proliferation.

Cited by 93 publications

References 27 publications

Exploring the biochemical mechanisms of cytotoxic gold compounds: a proteomic study

Exploring the biochemical mechanisms of cytotoxic gold compounds: a proteomic study

Peroxiredoxins, gerontogenes linking aging to genome instability and cancer

Tumor suppressor Prdx1 is a prognostic factor in esophageal squamous cell carcinoma patients

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