Role of NADPH oxidases in inducing a selective increase of oxidant stress and cyclin D1 and checkpoint 1 over-expression during progression to human gastric adenocarcinoma
| Autor: | Rolando Hernández-Muñoz, Diego Rolando Hernández-Espinosa, Agustín Echegaray-Donde, Edgar Mendieta-Condado, Juan Manuel Ruiz-Molina, Lourdes Sánchez-Sevilla, Julio Morán, Marisela Olguín-Martínez, Eduardo E. Montalvo-Javé, Martha Contreras-Zentella, Miguel F. Herrera, Luis F. Oñate-Ocaña, Tomás Escalante-Tatersfield |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Cancer Research Glutathione reductase Apoptosis Adenocarcinoma medicine.disease_cause Antioxidants Superoxide dismutase 03 medical and health sciences 0302 clinical medicine Cyclin D1 Stomach Neoplasms Gastric mucosa medicine Humans Cell Proliferation chemistry.chemical_classification Reactive oxygen species NADPH oxidase biology NADPH Oxidases Oxidants medicine.disease digestive system diseases Oxidative Stress 030104 developmental biology medicine.anatomical_structure Oncology chemistry Biochemistry Gastric Mucosa Case-Control Studies Caspases 030220 oncology & carcinogenesis Checkpoint Kinase 1 biology.protein Cancer research Female Reactive Oxygen Species Protein Kinases Oxidative stress |
| Zdroj: | European Journal of Cancer. 57:50-57 |
| ISSN: | 0959-8049 |
| DOI: | 10.1016/j.ejca.2015.11.027 |
| Popis: | Background Gastric cancer is one of the main causes of global mortality. Here, reactive oxygen species (ROS) could largely contribute to gastric carcinogenesis. Hence, the present work was aimed to assess the role of ROS, oxidant status, NADPH oxidases (NOXs) expression, during human gastric adenocarcinoma. Methods We obtained subcellular fraction from samples of gastric mucosa taken from control subjects (n = 20), and from 40 patients with gastric adenocarcinoma, as well as samples of distant areas (tumour-free gastric mucosa). Results Parameters indicative of lipid peroxidation and cell proliferation were selectively increased in both tumour-free and in cancerous gastric mucosa, despite of glutathione (GSH) content, glutathione reductase (GR) and superoxide dismutase (SOD) activities were increased in the adenocarcinoma. These high levels of antioxidant defences inversely correlated with down-regulated expression for NOX2 and 4; however, over-expression of NOX1 occurred with increased caspase-3 activity and overexpressed checkpoint 1 (MDC1) and cyclin D1 proteins. In the tumour-free mucosa an oxidant stress took place, without changing total GSH but with decreased activities for GR and mitochondrial SOD; moreover, over-expression of checkpoint 1 (MDC1) correlated with lower NOX2 and 4 expression in this mucosa. Conclusions Chronically injured gastric mucosa increases lipoperoxidative events and cell proliferation. In the adenocarcinoma, cell proliferation was further enhanced, oxidant stress decreased which seemed to be linked to NOX1, MDC1 and cyclin D1 over-expression, but with a lower NOXs activity leading a ‘low tone’ of ROS formation. Therefore, our results could be useful for early detection and treatment of gastric adenocarcinoma. |
| Databáze: | OpenAIRE |
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