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A metabolically stable analogue of anandamide, Met-F-AEA, inhibits human thyroid carcinoma cell lines by activation of apoptosis

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Summary

The active components of Cannabis sativa and their derivatives produce a wide spectrum of effects, some of which may have clinical application. The discovery of specific cannabinoid receptors and a family of endogenous ligands of those receptors has attracted much attention to cannabinoids as agents capable of controlling the decision of cells to survive or die. We analysed the effects exerted by 2-methyl-2′-F-anandamide (Met-F-AEA), a metabolically stable analogue of anandamide, and observed a growth inhibition in cell lines derived from thyroid carcinomas. Growth inhibition was associated with a high level of CB1 receptor expression, suggesting that the cytotoxic effect is due to interaction with the CB1 receptor. This phenomenon was associated with activation of the protein, p53, an increased apoptotic rate, and expression of p21CIP1/WAF1. This study provides new insights into the mechanism of Met-F-AEA action, and could have significance in providing a basis for the management of thyroid carcinoma.

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Acknowledgements

The authors thank Prof Vittorio Enrico Avvedimento for suggestions and for a critical review of the manuscript.

This work was supported by AIRC (Associazione Italiana per la Ricerca sul Cancro), Italy.

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Authors and Affiliations

  1. Department of Structural and Functional Biology, University of Naples “Federico II”, Via Cinthia, 80126, Naples, Italy

    Rosanna Cozzolino & Paolo Laccetti

  2. CNR-IEOS c/o Department of Cellular and Molecular Biology and Pathology ‘L. Califano’, University of Naples ‘Federico II’, Via Pansini 5, 80131, Naples, Italy

    Gaetano Calì

  3. Department of Pharmacology, University of Salerno, Via Ponte Don Melillo, Fisciano, 84084, Salerno, Italy

    Maurizio Bifulco

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  1. Rosanna Cozzolino
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  2. Gaetano Calì
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  4. Paolo Laccetti
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Correspondence to Paolo Laccetti.

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Cozzolino, R., Calì, G., Bifulco, M. et al. A metabolically stable analogue of anandamide, Met-F-AEA, inhibits human thyroid carcinoma cell lines by activation of apoptosis. Invest New Drugs 28, 115–123 (2010). https://doi.org/10.1007/s10637-009-9221-0

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