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Selective proapoptotic activity of polyphenols from red wine on teratocarcinoma cell, a model of cancer stem-like cell

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Summary

Cancer stem cells are expected to be responsible for tumor initiation and metastasis. These cells are therefore potential targets for innovative anticancer therapies. However, the absence of bona fide cancer stem cell lines is a real problem for the development of such approaches. Since teratocarcinoma cells are totipotent stem cells with a high degree of malignancy, we used them as a model of cancer stem cells in order to evaluate the anticancer chemopreventive activity of red wine polyphenols (RWPs) and to determine the underlying cellular and molecular mechanisms. We therefore investigated the effects of RWPs on the embryonal carcinoma (EC) cell line P19 which was grown in the same culture conditions as the most appropriate normal cell line counterpart, the pluripotent embryonic fibroblast cell line NIH/3T3. The present study indicates that RWPs selectively inhibited the proliferation of P19 EC cells and induced G1 cell cycle arrest in a dose-dependent manner. Moreover, RWPs treatment specifically triggered apoptosis of P19 EC cells in association with a dramatic upregulation of the tumor suppressor gene p53 and caspase-3 activation. Our findings suggest that the chemopreventive activity of RWPs on tumor initiation and development is related to a growth inhibition and a p53-dependent induction of apoptosis in teratocarcinoma cells. In addition, this study also shows that the EC cell line is a convenient source for studying the responses of cancer stem cells to new potential anticancer agents.

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Acknowledgments

This study has been supported by grants of the Ligue contre le Cancer (Comité du Haut-Rhin, France) and the Office National Interprofessionnel des Fruits, des Légumes, des Vins et de l’Horticulture (Action Vin et Santé, France). Tanveer Sharif is supported by a fellowship from the Higher Education Commission of Pakistan. Mahmoud Alhosin is supported by a fellowship from the Syrian Higher Education Ministry.

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Authors and Affiliations

  1. UMR 7213 CNRS, Laboratoire de Biophotonique et Pharmacologie, Université de Strasbourg, 74 route du Rhin, B.P. 60024, Illkirch, 67401, France

    Tanveer Sharif, Cyril Auger, Christian Bronner, Mahmoud Alhosin, Thibaut Klein, Nelly Etienne-Selloum, Valérie B. Schini-Kerth & Guy Fuhrmann

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  1. Tanveer Sharif
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  2. Cyril Auger
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Correspondence to Guy Fuhrmann.

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Sharif, T., Auger, C., Bronner, C. et al. Selective proapoptotic activity of polyphenols from red wine on teratocarcinoma cell, a model of cancer stem-like cell. Invest New Drugs 29, 239–247 (2011). https://doi.org/10.1007/s10637-009-9352-3

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