On the Promoting Action of Tamoxifen in the P-Dimethylaminoazobenzene Induced Hepatocarcinogenesis CF1 Mice Model and the Cytoprotective Role of Heme Oxygenase

Vázquez, Elba S.; Gerez, Esther Noemí; Caballero, Fabiana; Oliveri, Leda; Falcoff, Nora; Tomaro, Marı́a L.; Batlle, Alcira

doi:10.1007/978-1-4615-0741-3_42

Cited by 5 publications

(7 citation statements)

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“…The regulation of its potent enzymatic activity depends primarily on the control of HO-1 expression at transcriptional level (Alam et al, 2004;Dulak et al, 2004). The role of HO-1 in tissue pathology is determined either by a delicate balance between the injurious and protective action of the end products generated during haeme catabolism (Dong et al, 2000) or by exerting a function distinct from haeme degradation (Vazquez et al, 2002) and playing a more proactive role in physiological and pathological processes (Willis, 1999;Maines, 2000). Hence, the induction of HO-1 is one of the most important events in cellular response to pro-oxidative and proinflammatory insults (Prawan et al, 2005).…”

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confidence: 99%

Nuclear translocation of haeme oxygenase-1 is associated to prostate cancer

et al. 2007

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The role of oxidative stress in prostate cancer has been increasingly recognised. Acute and chronic inflammations generate reactive oxygen species that result in damage to cellular structures. Haeme oxygenase-1 (HO-1) has cytoprotective effects against oxidative damage. We hypothesise that modulation of HO-1 expression may be involved in the process of prostate carcinogenesis and prostate cancer progression. We thus studied HO-1 expression and localisation in 85 samples of organ-confined primary prostate cancer obtained via radical prostatectomy (Gleason grades 4 -9) and in 39 specimens of benign prostatic hyperplasia (BPH). We assessed HO-1 expression by immunohistochemical staining. No significant difference was observed in the cytoplasmic positive reactivity among tumours (84%), non-neoplastic surrounding parenchyma (89%), or BPH samples (87%) (P ¼ 0.53). Haeme oxygenase-1 immunostaining was detected in the nuclei of prostate cancer cells in 55 of 85 (65%) patients but less often in nonneoplastic surrounding parenchyma (30 of 85, 35%) or in BPH (9 of 39, 23%) (Po0.0001). Immunocytochemical and western blot analysis showed HO-1 only in the cytoplasmic compartment of PC3 and LNCaP prostate cancer cell lines. Treatment with hemin, a well-known specific inducer of HO-1, led to clear nuclear localisation of HO-1 in both cell lines and highly induced HO-1 expression in both cellular compartments. These findings have demonstrated, for the first time, that HO-1 expression and nuclear localisation can define a new subgroup of prostate cancer primary tumours and that the modulation of HO-1 expression and its nuclear translocation could represent new avenues for therapy.

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Nuclear translocation of haeme oxygenase-1 is associated to prostate cancer

et al. 2007

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“…We have previously reported increased HO-1 expression in DAB fed animals [10] as consequence of the oxidative stress provoked by the carcinogen [19]. Furthermore, we have studied this protein expression and cellular localization during the different stages of HC [14].…”

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confidence: 99%

“…The regulation of its potent enzymatic activity depends primarily on the control of HO-1 expression at transcriptional level [23,25]. HO-1 induction is considered to be an adaptative cellular response to oxidative stress [26,19]. Up-regulation of HO-1 expression in DAB fed animals, as an endogenous antioxidant defense mechanism, would serve as a protective factor controlling the changes associated to the carcinogenic process [19,14].…”

Section: Discussionmentioning

confidence: 99%

“…HO-1 induction is considered to be an adaptative cellular response to oxidative stress [26,19]. Up-regulation of HO-1 expression in DAB fed animals, as an endogenous antioxidant defense mechanism, would serve as a protective factor controlling the changes associated to the carcinogenic process [19,14]. We demonstrated that HO-1 levels were diminished in HR group in comparison with animals that received a continuous carcinogenic diet, indicating that deprivation of the carcinogen will promote hepatic regeneration and enable to restore the hepatic homeostasis.…”

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confidence: 99%

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Homeostatic response under carcinogen withdrawal, heme oxygenase 1 expression and cell cycle association

et al. 2006

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Background: Chronic injury deregulates cellular homeostasis and induces a number of alterations leading to disruption of cellular processes such as cell cycle checkpoints and apoptosis, driving to carcinogenesis. The stress protein heme oxygenase-1 (HO-1) catalyzes heme degradation producing biliverdin, iron and CO. Induction of HO-1 has been suggested to be essential for a controlled cell growth. The aim of this work was to analyze the in vivo homeostatic response (HR) triggered by the withdrawal of a potent carcinogen, p-dimethylaminoazobenzene (DAB), after preneoplastic lesions were observed. We analyzed HO-1 cellular localization and the expression of HO-1, Bcl-2 and cell cycle related proteins under these conditions comparing them to hepatocellular carcinoma (HC).

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“…We have shown that HO‐1 mRNA levels were greatly induced in the liver of DAB‐treated animals, and that this level of induction persisted as long as the oxidative damage lasted. However, HO activity would be modulated by post‐transcriptional events (Vazquez et al . 2002).…”

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Immunohistochemical analysis of heme oxygenase‐1 in preneoplastic and neoplastic lesions during chemical hepatocarcinogenesis^§

Caballero

Meiss

Giménez

et al. 2004

Int J Experimental Path

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Heme oxygenase (HO) breaks down the pro-oxidant heme into carbon monoxide, iron and the antioxidant biliverdin. The isoform HO-1 plays an effective role to counteract oxidative damage and to control inflammation. Prolonged cellular damage due to chronic inflammation is one of the reasons leading to the development of tumours. The aim of this work was to investigate HO-1 expression and localization along the different stages of chemically induced hepatocarcinogenesis (HCC) and the occurring morphological changes. To provoke sustained oxidative stress and chronic inflammation, CF1 mice received dietary p-dimethylaminoazobenzene (DAB, 0.5%, w/w) during a whole period of 14 months. HO-1 expression increased along the experimental trial in morphologically normal hepatocytes in DAB-treated animals. HO-1 expression diminished in altered hepatic foci (AHF) and oval cells and early preneoplastic lesions. Otherwise, marked HO-1 overexpression was detected in Kupffer cells and macrophages surrounding necrotic and nodular areas. Adenomas showed decreased HO-1 immunostaining. In hepatocellular carcinomas, an inverse relationship was found between the immunohistochemical expression of HO-1 and the degree of tumour differentiation, being negative in poorly differentiated tumours. In our experimental model, down modulation of HO-1 expression correlated with malignancy progression. Thus, our data point to activation of HO-1 as a potential therapeutic tool.

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On the Promoting Action of Tamoxifen in the P-Dimethylaminoazobenzene Induced Hepatocarcinogenesis CF1 Mice Model and the Cytoprotective Role of Heme Oxygenase

Cited by 5 publications

References 31 publications

Nuclear translocation of haeme oxygenase-1 is associated to prostate cancer

Nuclear translocation of haeme oxygenase-1 is associated to prostate cancer

Homeostatic response under carcinogen withdrawal, heme oxygenase 1 expression and cell cycle association

Immunohistochemical analysis of heme oxygenase‐1 in preneoplastic and neoplastic lesions during chemical hepatocarcinogenesis^§

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On the Promoting Action of Tamoxifen in the P-Dimethylaminoazobenzene Induced Hepatocarcinogenesis CF1 Mice Model and the Cytoprotective Role of Heme Oxygenase

Cited by 5 publications

References 31 publications

Nuclear translocation of haeme oxygenase-1 is associated to prostate cancer

Nuclear translocation of haeme oxygenase-1 is associated to prostate cancer

Homeostatic response under carcinogen withdrawal, heme oxygenase 1 expression and cell cycle association

Immunohistochemical analysis of heme oxygenase‐1 in preneoplastic and neoplastic lesions during chemical hepatocarcinogenesis§

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Immunohistochemical analysis of heme oxygenase‐1 in preneoplastic and neoplastic lesions during chemical hepatocarcinogenesis^§