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Role of melatonin in the epigenetic regulation of breast cancer

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Abstract

The oncostatic properties of melatonin as they directly or indirectly involve epigenetic mechanisms of cancer are reviewed with a special focus on breast cancer. Five lines of evidence suggest that melatonin works via epigenetic processes: (1) melatonin influences transcriptional activity of nuclear receptors (ERα, GR and RAR) involved in the regulation of breast cancer cell growth; (2) melatonin down-regulates the expression of genes responsible for the local synthesis or activation of estrogens including aromatase, an effect which may be mediated by methylation of the CYP19 gene or deacetylation of CYP19 histones; (3) melatonin inhibits telomerase activity and expression induced by either natural estrogens or xenoestrogens; (4) melatonin modulates the cell cycle through the inhibition of cyclin D1 expression; (5) melatonin influences circadian rhythm disturbances dependent on alterations of the light/dark cycle (i.e., light at night) with the subsequent deregulation of PER2 which acts as a tumor suppressor gene.

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Acknowledgements

This work is supported in part by a grant from the Spanish Ministry of Education and Science (SAF2007-62762).

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Authors and Affiliations

  1. Department of Physiology, School of Medicine, Gulhane Military Medical Academy, Ankara, Turkey

    Ahmet Korkmaz

  2. Department of Cellular and Structural Biology, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX, 78229, USA

    Ahmet Korkmaz, Dun-Xian Tan & Russel J. Reiter

  3. Department of Physiology and Pharmacology, School of Medicine, University of Cantabria, Santander, Spain

    Emilio J. Sanchez-Barcelo

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  1. Ahmet Korkmaz
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Correspondence to Ahmet Korkmaz.

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Korkmaz, A., Sanchez-Barcelo, E.J., Tan, DX. et al. Role of melatonin in the epigenetic regulation of breast cancer. Breast Cancer Res Treat 115, 13–27 (2009). https://doi.org/10.1007/s10549-008-0103-5

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