Effects of heme oxygenase-1 on induction and development of chemically induced squamous cell carcinoma in mice

Waś, Halina; Sokołowska, Małgorzata; Sierpniowska, Aleksandra; Dominik, Pawel K.; Skrzypek, Klaudia; Lackowska, B; Pratnicki, A; Grochot-Przęczek, Anna; Taha, Hevidar; Kotlinowski, Jerzy; Kozakowska, Magdalena; Mazan, Andrzej; Nowak, Witold; Muchová, Lucie; Vı́tek, Libor; Ratajska, Anna; Dulak, Józef; Józkowicz, Alicja

doi:10.1016/j.freeradbiomed.2011.07.025

Cited by 43 publications

(35 citation statements)

References 54 publications

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“…Unfortunately, tumor progression could not be analyzed in the HPV8 model, as the rate of malignant conversion is generally low in these mice (22) and as the animals had to be eliminated due to the tumor size before malignant conversion had occurred. The result seen in the DMBA/TPA model is consistent with results obtained with mice lacking the antioxidant enzyme heme oxygenase-1, which were characterized by enhanced skin tumorigenesis, but reduced tumor progression upon application of the same tumorigenesis protocol (41). The most likely explanation is a protection from ROS-induced apoptosis of tumor cells by the overexpressed Prdx6 (Fig.…”

Section: Discussionsupporting

confidence: 88%

Dual Role of the Antioxidant Enzyme Peroxiredoxin 6 in Skin Carcinogenesis

et al. 2013

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The antioxidant enzyme peroxiredoxin 6 (Prdx6) is a key regulator of the cellular redox balance, particularly under stress conditions. We identified Prdx6 as an important player in different phases of skin carcinogenesis. Loss of Prdx6 in mice enhanced the susceptibility to skin tumorigenesis, whereas overexpression of Prdx6 in keratinocytes of transgenic mice had the opposite effect. The tumor-preventive effect of Prdx6, which was observed in a human papilloma virus 8-induced and a chemically induced tumor model, was not due to alterations in keratinocyte proliferation, apoptosis, or in the inflammatory response. Rather, endogenous and overexpressed Prdx6 reduced oxidative stress as reflected by the lower levels of oxidized phospholipids in the protumorigenic skin of Prdx6 transgenic mice and the higher levels in Prdx6-knockout mice than in control animals. In contrast to its beneficial effect in tumor prevention, overexpression of Prdx6 led to an acceleration of malignant progression of existing tumors, revealing a dual function of this enzyme in the pathogenesis of skin cancer. Finally, we found strong expression of PRDX6 in keratinocytes of normal human skin and in the tumor cells of squamous cell carcinomas, indicating a role of Prdx6 in human skin carcinogenesis. Taken together, our data point to the potential usefulness of Prdx6 activators or inhibitors for controlling different stages of skin carcinogenesis. Cancer Res; 73(11); 3460-9. Ó2013 AACR.

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Section: Discussionsupporting

confidence: 88%

Dual Role of the Antioxidant Enzyme Peroxiredoxin 6 in Skin Carcinogenesis

et al. 2013

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“…Anti-inflammatory [116,120] Anti-oxidant [133] Anti-apoptotic [116] Anti-mutagenic [119] Anti-exitotxic [156] Anti-complement [25] Anti-nitrosative [45,123] Cytoprotective [35] Numerous reviews have been written about the unquestionable toxicity of bilirubin at high concentrations [143]. However, mild physiological jaundice is no longer considered a threat [144]. Hyperbilirubinemia in neonates should long since have been considered as a transitional mechanism in neonatal circulation, where high bilirubin levels provide back up to the neonate with a weak immune system and antioxidant defense.…”

Section: Resultsmentioning

confidence: 99%

The pharmacological features of bilirubin: the question of the century

Zahir

Rabbani

Khan

et al. 2015

Cellular and Molecular Biology Letters

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This review looks at the toxicity and metabolism of bilirubin in terms of its pharmacological potential. Its role has gained importance as more research has revealed the functional significance and interrelationship between the gasotransmitters nitric oxide and carbon monoxide. The biological actions of bilirubin have mostly been characterized in the high micromolar range where toxic effects occur. However, it could also prove to be an important cytoprotector for brain tissue, which is inherently less equipped for antioxidant defense. Plasma bilirubin levels negatively correlate to a number of disease states. Higher levels of bilirubin that are still within the normal range provide a protective effect to the body. The effects on various disorders could be tested using controlled pharmacological upregulation of the molecule with animal models. At nanomolar concentrations, considerable benefits have been obtained when the molecule was delivered pharmacologically under in vitro or in vivo test conditions, particularly in neurodegenerative disorders and after tissue or organ transplantation. The induction of heme oxygenase-1 (HMOX-1) via the activation of nuclear factor erythroid 2-related factor or the use of bile pigments in the harvesting of diseased tissue are novel applications, and like every new therapy, should be used with caution. HMOX-1 is tissue specific, and in exceptional states, such as schizophrenia and specific types of renal disorder, the same therapy may have disastrous effects.

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“…These conflicting findings may be related to the diverse roles of HO1 in various conditions or the status of the cells during tumorigenesis. HO1 may be protective for healthy cells in tumor-inducing injury; however, it could be tumor progressive in already developed tumors [45]. Therefore, further study is needed to explore the exact role(s) of HO1 and its possible correlation with NGF in BRCA tumorigenesis.…”

Section: Discussionmentioning

confidence: 99%

Expression of nerve growth factor and heme oxygenase-1 predict poor survival of breast carcinoma patients

et al. 2013

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BackgroundNerve growth factor (NGF) is a neurotrophin and has been suggested to induce heme oxygenase-1 (HO1) expression. Although the role of HO1 in tumorigenesis remains controversial, recent evidence suggests NGF and HO1 as tumor-progressing factors. However, the correlative role of NGF and HO1 and their prognostic impact in breast carcinoma is unknown.MethodsWe investigated the expression and prognostic significance of the expression of NGF and HO1 in 145 cases of breast carcinoma.ResultsImmunohistochemical expression of NGF and HO1 was observed in 31% and 49% of breast carcinoma, respectively. The expression of NGF and HO1 significantly associated with each other, and both have a significant association with histologic grade, HER2 expression, and latent distant metastasis. The expression of NGF and HO1 predicted shorter overall survival of breast carcinoma by univariate and multivariate analysis. NGF expression was an independent prognostic indicator for relapse-free survival by multivariate analysis. The combined expression pattern of NGF and HO1 was also an independent prognostic indicator of overall survival and relapse-free survival. The patients with tumors expressing NGF had the shortest survival and the patients with tumor, which did not express NGF or HO1 showed the longest survival time.ConclusionsThis study has demonstrated that individual expression of NGF or HO1, and the combined NGF/HO1 expression pattern could be prognostic indicators for breast carcinoma patients.

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Effects of heme oxygenase-1 on induction and development of chemically induced squamous cell carcinoma in mice

Cited by 43 publications

References 54 publications

Dual Role of the Antioxidant Enzyme Peroxiredoxin 6 in Skin Carcinogenesis

Dual Role of the Antioxidant Enzyme Peroxiredoxin 6 in Skin Carcinogenesis

The pharmacological features of bilirubin: the question of the century

Expression of nerve growth factor and heme oxygenase-1 predict poor survival of breast carcinoma patients

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