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Chronic stress decreases ornithine decarboxylase expression and protects against 1,2-dimethylhydrazine-induced colon carcinogenesis

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Abstract

Biological response to stress depends on the type, timing, and severity of the stressor. Acute stressful environments may positively activate molecular and cellular mechanisms to favor adaptation; however, chronic stress is often associated with detrimental health effects. Colon cancer (CC) is one of the leading causes of death associated with cancer and has been mentioned as a stress-related disease. In the present work, the effect of chronic stress on the initial phase of CC was evaluated, and special emphasis was placed on ornithine decarboxylase (ODC) expression and polyamines for their role in hyperproliferative diseases. BALB/c mice (n = 5/group) were administered the pro-carcinogen 1,2-dimethylhydrazine (DMH) for 8 weeks (20 mg/kg body weight/week) to induce colon carcinogenesis, and then exposed for 4 weeks to two physical stressors: restraint and forced-swimming. Distal colon inflammatory lesions and histomorphological changes were evaluated by hematoxylin–eosin staining; plasma corticosterone levels, colon ODC expression, and urinary polyamines were determined by competitive ELISA, RT-qPCR, Western Blot, and HPLC, respectively. The short-term exposure to DMH triggered colon inflammation, initiated colon carcinogenesis and increased ODC expression; meanwhile, the exposure to chronic stress activated the hypothalamic–pituitary–adrenal (HPA) axis, elicited the production of plasmatic corticosterone, and decreased ODC expression. The exposure of DMH-treated mice to chronic stress counteracted the inflammatory effect of DMH and maintained ODC homeostasis. In early phase of carcinogenesis, the exposure of DMH-treated mice to chronic stress had a positive effect against colon inflammation and maintained ODC homeostasis. The cross-talk between corticosterone, ODC expression, and inflammation in a tumor environment is discussed.

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Acknowledgements

Our special thanks to MD Felipe Cerda-Camacho, and Dr. David Avila-Figueroa, for histopathological evaluations; and to María Jazmin Gutiérrez Zepeda for English language editing of the manuscript.

Funding

This study was supported by funding from the P3E and Research Programs from the University of Guadalajara, México (#249947), PFCE-SEP (Programa de Fortalecimiento de la Calidad Educativa- Secretaria de la Educación Pública).

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Authors and Affiliations

  1. Departamento de Bienestar y Desarrollo Sustentable, Centro Universitario del NORTE, Carretera Federal No. 23, Km 191, C.P. 46200, Colotlán, Jalisco, México

    Edgar Oswaldo Zamora-González

  2. Departamento de Biología Celular y Molecular, Centro Universitario de Ciencias Biológicas y Agropecuarias, Carretera Guadalajara-Nogales Km 15.5, Las Agujas, C.P. 45110, Zapopan, Jalisco, México

    Patricia Castro-Félix, María del Rosario Huizar-López, Josefina Casas-Solís, María de la Luz Blanca Isabel Marques-González & Anne Santerre

  3. Departamento de Fundamentos del Conocimiento, Centro Universitario del NORTE, Carretera Federal No. 23, Km 191, C.P. 46200, Colotlán, Jalisco, México

    Martha Fabiola Martin del Campo-Solís

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  1. Edgar Oswaldo Zamora-González
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  2. Patricia Castro-Félix
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Contributions

EOZG and AS participated in the design of the experiments. EOZG, MLBIMG, and AS contributed to the experiments. All authors contributed to the analysis and discussion of the results, and preparation of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Anne Santerre.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed, and all procedures performed in studies involving animals were conducted following the ethical standards of the University of Guadalajara, Mexico. Ethical approval was granted by the Ethical Committee of the Research Coordination of the Campus of Agricultural and Biological Sciences (CUCBA) of the University of Guadalajara, Jalisco, México (C.INV./104/2020).

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Zamora-González, E.O., Castro-Félix, P., Huizar-López, M.R. et al. Chronic stress decreases ornithine decarboxylase expression and protects against 1,2-dimethylhydrazine-induced colon carcinogenesis. Mol Biol Rep 47, 9429–9439 (2020). https://doi.org/10.1007/s11033-020-06022-0

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