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Melatonin triggers p53Ser phosphorylation and prevents DNA damage accumulation

Oncogene volume 31, pages 2931–2942 (2012)Cite this article

Abstract

Several epidemiological studies have shown that high levels of melatonin, an indolic hormone secreted mainly by the pineal gland, reduce the risks of developing cancer, thus suggesting that melatonin triggers the activation of tumor-suppressor pathways that lead to the prevention of malignant transformation. This paper illustrates that melatonin induces phosphorylation of p53 at Ser-15 inhibiting cell proliferation and preventing DNA damage accumulation of both normal and transformed cells. This activity requires p53 and promyelocytic leukemia (PML) expression and efficient phosphorylation of p53 at Ser-15 residue. Melatonin-induced p53 phosphorylation at Ser-15 residue does not require ataxia telangiectasia-mutated activity, whereas it is severely impaired upon chemical inhibition of p38 mitogen-activated protein kinase activity. By and large, these findings imply that the activation of the p53 tumor-suppressor pathway is a critical mediator of melatonin and its anticancer effects. Therefore, it provides molecular insights into increasing observational evidence for the role that melatonin has in cancer prevention.

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Acknowledgements

We thank Dr E O’Neill and Dr Y Shiloh for gift of reagents and cell lines. Moreover, we also thank T Merlino for kindly revising the English text. This study was supported by Associazione Italiana Ricerca sul Cancro (AIRC, to SS and GB), Ministero della Salute (GB and PM), Fondazione Veronesi (GB), FIRB (GB), New Idea Award (SS) and Fondazione Italiana Ricerca sul Cancro (FIRC, fellowship to RS).

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Authors and Affiliations

  1. Molecular Medicine Department, Molecular Chemoprevention Group, Italian National Cancer Institute ‘Regina Elena’, Rome, Italy

    R Santoro, M Marani & S Strano

  2. Molecular Medicine Department, Translational Oncogenomic Unit-ROC, Italian National Cancer Institute ‘Regina Elena’, Rome, Italy

    G Blandino

  3. Scientific Director Office, Italian National Cancer Institute ‘Regina Elena’, Rome, Italy

    P Muti

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  1. R Santoro
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  2. M Marani
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Correspondence to S Strano.

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Santoro, R., Marani, M., Blandino, G. et al. Melatonin triggers p53Ser phosphorylation and prevents DNA damage accumulation. Oncogene 31, 2931–2942 (2012). https://doi.org/10.1038/onc.2011.469

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