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Hydroxytyrosol inhibits growth and cell proliferation and promotes high expression of sfrp4 in rat mammary tumours

Authors

  • Sergio Granados-Principal,

    1. Department of Biochemistry and Molecular Biology II, University of Granada, Granada, Spain
    2. “José Mataix” Institute of Nutrition and Food Technology, Biomedical Research Centre, Health Sciences Technological Park, University of Granada, Granada, Spain
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  • Jose L. Quiles,

    1. “José Mataix” Institute of Nutrition and Food Technology, Biomedical Research Centre, Health Sciences Technological Park, University of Granada, Granada, Spain
    2. Department of Physiology, University of Granada, Granada, Spain
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  • Cesar Ramirez-Tortosa,

    1. Pathological Anatomy Service, Jaen City Hospital, Jaen, Spain
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  • Pedro Camacho-Corencia,

    1. “José Mataix” Institute of Nutrition and Food Technology, Biomedical Research Centre, Health Sciences Technological Park, University of Granada, Granada, Spain
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  • Pedro Sanchez-Rovira,

    1. Oncology Service, Jaen City Hospital, Jaen, Spain
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  • Laura Vera-Ramirez,

    1. Oncology Service, Jaen City Hospital, Jaen, Spain
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  • MCarmen Ramirez-Tortosa

    Corresponding author
    1. Department of Biochemistry and Molecular Biology II, University of Granada, Granada, Spain
    2. “José Mataix” Institute of Nutrition and Food Technology, Biomedical Research Centre, Health Sciences Technological Park, University of Granada, Granada, Spain
    • Instituto de Nutrición y Tecnología de Alimentos “José Mataix Verdú”. Universidad de Granada. Centro de Investigación Biomédica. Parque Tecnológico de Ciencias de la Salud. Avenida del Conocimiento s/n, 18100-Granada, Spain Fax: +34-958819132
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Abstract

Scope: Hydroxytyrosol (a phenolic compound derived from virgin olive oil) has demonstrated an anti-tumour effect in several tumour cell lines in addition to other health-related properties. The aim of this study was to investigate, for the first time in an animal model of experimental mammary carcinoma, the anti-cancer ability of hydroxytyrosol and to discover which pathways are modified by hydroxytyrosol.

Methods and results: Dimethylbenz[α]anthracene-induced mammary tumours were induced in 28 female Sprague–Dawley rats and ten of them were treated with hydroxytyrosol (0.5 mg/kg b.w. 5 days/week for 6 wk). cDNA microarray and quantitative RT-PCR experiments were performed. Hydroxytyrosol was found to inhibit the experimental mammary tumour growth and proliferation rate, with results comparable to those of doxorubicin but better with regard to the histopathological outcome. It also altered the expression of genes related to apoptosis, cell cycle, proliferation, differentiation, survival and transformation pathways.

Conclusions: This study shows that hydroxytyrosol exerts anti-cancer effects in Sprague–Dawley rats with experimental mammary tumours, inhibiting growth and cell proliferation in mammary tumours. Moreover, hydroxytyrosol alters several genes associated with cell proliferation, apoptosis and the Wnt signalling pathway, promoting a high expression of Sfrp4. However, further studies are necessary to better understand the mechanisms of hydroxytyrosol.

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