RESUMO
Tobacco can induce reactive oxygen species (ROS) production extensively in cells, which is a major risk factor for oral leukoplakia (OLK) development. Peroxiredoxin 1 (Prx1) is a key antioxidant protein, upregulated in a variety of malignant tumors. We previously found that nicotine, the main ingredient of tobacco, promotes oral carcinogenesis via regulating Prx1. The aim of the present study was to screen and identify the Prx1 interacting proteins and investigate the mechanisms of nicotine on the development of OLK. Through liquid chromatography-tandem mass spectrometry combined with bioinformatics analysis, the candidate Prx1 interacting proteins of cofilin-1 (CFL1), tropomyosin alpha-3 chain (TPM3), and serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform (PPP2R1A) were screened in human dysplastic oral keratinocyte cells treated with nicotine. CFL1, TPM3, and PPP2R1A were highly expressed in human OLK tissues. The expression of CFL1 increased and the expression of PPP2R1A decreased in OLK of smokers compared to that in OLK of non-smokers. Nicotine upregulated CFL1 and downregulated PPP2R1A in 4-nitro-quinoline-1-oxide (4NQO)-induced OLK tissues in mice in part dependent on Prx1. Furthermore, the in-situ interaction of CFL1, TPM3, and PPP2R1A with Prx1 were validated in human OLK tissues. Our results suggested that tobacco might promote the development of OLK via regulating Prx1 and its interacting proteins CFL1 and PPP2R1A.
Assuntos
Leucoplasia Oral , Nicotina , Peroxirredoxinas , Animais , Carcinogênese , Proteínas de Transporte , Proteínas de Homeodomínio , Leucoplasia Oral/induzido quimicamente , Camundongos , Peroxirredoxinas/metabolismoRESUMO
Tobacco can induce reactive oxygen species (ROS) production extensively in cells, which is a major risk factor for oral leukoplakia (OLK) development. Peroxiredoxin 1 (Prx1) is a key antioxidant protein, upregulated in a variety of malignant tumors. We previously found that nicotine, the main ingredient of tobacco, promotes oral carcinogenesis via regulating Prx1. The aim of the present study was to screen and identify the Prx1 interacting proteins and investigate the mechanisms of nicotine on the development of OLK. Through liquid chromatography-tandem mass spectrometry combined with bioinformatics analysis, the candidate Prx1 interacting proteins of cofilin-1 (CFL1), tropomyosin alpha-3 chain (TPM3), and serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform (PPP2R1A) were screened in human dysplastic oral keratinocyte cells treated with nicotine. CFL1, TPM3, and PPP2R1A were highly expressed in human OLK tissues. The expression of CFL1 increased and the expression of PPP2R1A decreased in OLK of smokers compared to that in OLK of non-smokers. Nicotine upregulated CFL1 and downregulated PPP2R1A in 4-nitro-quinoline-1-oxide (4NQO)-induced OLK tissues in mice in part dependent on Prx1. Furthermore, the in-situ interaction of CFL1, TPM3, and PPP2R1A with Prx1 were validated in human OLK tissues. Our results suggested that tobacco might promote the development of OLK via regulating Prx1 and its interacting proteins CFL1 and PPP2R1A.
Assuntos
Animais , Camundongos , Leucoplasia Oral/induzido quimicamente , Peroxirredoxinas/metabolismo , Nicotina , Proteínas de Transporte , Proteínas de Homeodomínio , CarcinogêneseRESUMO
PURPOSE: The aim of this study was to evaluate whether sleep restriction (SR) could affect the mechanisms and pathways' essentials for cancer cells in tongue cancer induced by 4-nitroquinoline 1-oxide in Wistar rats. METHODS: The animals were distributed into 4 groups of 5 animals each treated with 50 ppm 4 NQO solution through their drinking water for 4 and 12 weeks. The animals were submitted to sleep restriction for 21 days using the modified multiple platform method, which consisted of placing 5 rats in a cage (41 × 34 × 16 cm) containing 10 circular platforms (3.5 cm in diameter) with water 1 cm below the upper surface. The investigations were conducted using immunohistochemistry of p53, Bax and Bcl-2 proteins related to apoptosis and its pathways. RESULTS: Although no histopathologic abnormalities were induced in the epithelium after 4 weeks of carcinogen exposure in all groups, in 12 weeks were observed pre-neoplastic lesions. Data analysis revealed statistically significant differences (P < 0.05) in 4 weeks group for p53, and for bcl-2. Following 12 weeks of 4NQO administration, we found significant differences between SR and control groups in p53, bax, and bcl-2 immunoexpression. CONCLUSION: Our results reveal that sleep restriction exerted alterations in proteins associated with proliferation and apoptosis in carcinogenesis.
Assuntos
Proteínas Reguladoras de Apoptose/análise , Carcinogênese , Proteínas Proto-Oncogênicas c-bcl-2/análise , Sono/fisiologia , Neoplasias da Língua/induzido quimicamente , Proteína Supressora de Tumor p53/análise , Proteína X Associada a bcl-2/análise , 4-Nitroquinolina-1-Óxido/efeitos adversos , Animais , Apoptose/efeitos dos fármacos , Carcinogênese/efeitos dos fármacos , Carcinógenos , Proliferação de Células/efeitos dos fármacos , Epitélio/química , Epitélio/efeitos dos fármacos , Leucoplasia Oral/induzido quimicamente , Leucoplasia Oral/química , Masculino , Lesões Pré-Cancerosas/induzido quimicamente , Lesões Pré-Cancerosas/química , Quinolonas/efeitos adversos , Distribuição Aleatória , Ratos , Ratos Wistar , Transtornos do Sono-Vigília/metabolismo , Fatores de Tempo , Neoplasias da Língua/químicaRESUMO
BACKGROUND: Most studies have demonstrated 4-NQO toxicity to oral epithelium during oral carcinogenesis induction, but systemic toxicity has been poorly addressed. The aim of this study was to describe the systemic effect of 4-NQO topical application during early phases of oral cancer induction. METHODS: A 4-NQO propylene glycol ointment was topically applied on the rat tongue three times a week for 16 weeks. Local and systemic 4-NQO toxicity was evaluated by body weight gain, hematology, and serum chemistry analyses, histopathology, and proliferating cell nuclear antigen (PCNA) immunohistochemistry. RESULTS: Significant reduction in body weight gain and in white blood cell count as well as significant increase in serum ALT and AST was observed after 16 weeks of 4-NQO topical application. Focal hepatic lobular necrosis, renal tubular degeneration, and decreased cellularity in the splenic white pulp were also detected. CONCLUSIONS: 4-NQO topical application on the tongue of rats for 16 weeks seems to have caused hepatic, renal, and splenic toxicity. Potential systemic toxicity should be considered to monitor for variables that could interfere in topical oral carcinogenesis experiments.
Assuntos
Carcinogênese/induzido quimicamente , Carcinógenos/toxicidade , Quinolonas/toxicidade , 4-Nitroquinolina-1-Óxido/toxicidade , Administração Tópica , Alanina Transaminase/sangue , Alanina Transaminase/efeitos dos fármacos , Animais , Aspartato Aminotransferases/sangue , Aspartato Aminotransferases/efeitos dos fármacos , Análise Química do Sangue , Feminino , Queratinócitos/efeitos dos fármacos , Túbulos Renais/efeitos dos fármacos , Contagem de Leucócitos , Leucoplasia Oral/induzido quimicamente , Fígado/efeitos dos fármacos , Monócitos/efeitos dos fármacos , Pâncreas/efeitos dos fármacos , Lesões Pré-Cancerosas/induzido quimicamente , Antígeno Nuclear de Célula em Proliferação/efeitos dos fármacos , Ratos , Ratos Wistar , Albumina Sérica/efeitos dos fármacos , Baço/citologia , Baço/efeitos dos fármacos , Glândula Submandibular/efeitos dos fármacos , Língua/efeitos dos fármacos , Neoplasias da Língua/induzido quimicamente , Aumento de Peso/efeitos dos fármacosRESUMO
This report deals with endemic chronic arsenical intoxication (HACRE) observed in several provinces in Argentina. Similar reports come from Chili, Mexico, Brasil, Bolivia, Peru and Japan. HACRE patients show no systemic, symptoms and specific manifestations are palmoplantar keratoderma, multiple cutaneous epitheliomas, mainly Bowen-type and respiratory or digestive carcinomas. The authors emphasize that these specific manifestations of HACRE are worth knowing for their possible social incidence.