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Combining naturally occurring polyphenols with TNF-related apoptosis-inducing ligand: a promising approach to kill resistant cancer cells?

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Abstract

TNF-related apoptosis-inducing ligand (TRAIL) and its receptors are attractive targets for anticancer therapy owing to their ability to trigger apoptosis selectively in cancer cells but not in normal cells. To date, many combinatorial strategies, such as chemotherapy or radiotherapy, have given encouraging results for overcoming TRAIL resistance in preclinical models. In this review, we provide an overview of the molecular mechanisms underlying sensitization to TRAIL-induced apoptosis by polyphenols. These naturally occurring compounds can restore tumor cell sensitivity to TRAIL-induced cell death with no apparent toxicity towards normal cells. Both extrinsic and intrinsic pathways can be modulated by polyphenols, the activation of which largely depends on the cell type, the particular polyphenolic compound, and the conditions of treatment. The large variety of polyphenol cellular targets could prove useful in circumventing TRAIL resistance. The relevance of these combined treatments for cancer therapy is discussed in the light of recent preclinical studies.

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Acknowledgments

This work was supported by grants of the Conseil Regional de Bourgogne, the INCa (Institut National du Cancer) Canceropôle Grand-Est, ANR (Agence Nationale de la Recherche, ANR-06-JCJC-0103 and 07-PCV-0031) and the European Community (ApopTrain Marie Curie RTN) (O.M.). G.J. is supported by a fellowship from the Ligue Nationale Contre le Cancer. S.S. is supported by the INCa (POLYNOM-174).

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Jacquemin, G., Shirley, S. & Micheau, O. Combining naturally occurring polyphenols with TNF-related apoptosis-inducing ligand: a promising approach to kill resistant cancer cells?. Cell. Mol. Life Sci. 67, 3115–3130 (2010). https://doi.org/10.1007/s00018-010-0407-6

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  • DOI: https://doi.org/10.1007/s00018-010-0407-6

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