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Int. J. Mol. Sci. 2017, 18(10), 2160;

Impact of Natural Compounds on DNA Methylation Levels of the Tumor Suppressor Gene RASSF1A in Cancer

Institute for Genetics, Justus-Liebig-University Giessen, D-35392 Giessen, Germany
German Center for Lung Research (DZL), Universities of Giessen and Marburg Lung Center, D-35392 Giessen, Germany
Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Colombo, Colombo 0080, Sri Lanka
Author to whom correspondence should be addressed.
Received: 1 September 2017 / Revised: 28 September 2017 / Accepted: 12 October 2017 / Published: 17 October 2017
(This article belongs to the Special Issue DNA Methylation)
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Epigenetic inactivation of tumor suppressor genes (TSG) is a fundamental event in the pathogenesis of human cancer. This silencing is accomplished by aberrant chromatin modifications including DNA hypermethylation of the gene promoter. One of the most frequently hypermethylated TSG in human cancer is the Ras Association Domain Family 1A (RASSF1A) gene. Aberrant methylation of RASSF1A has been reported in melanoma, sarcoma and carcinoma of different tissues. RASSF1A hypermethylation has been correlated with tumor progression and poor prognosis. Reactivation of epigenetically silenced TSG has been suggested as a therapy in cancer treatment. In particular, natural compounds isolated from herbal extracts have been tested for their capacity to induce RASSF1A in cancer cells, through demethylation. Here, we review the treatment of cancer cells with natural supplements (e.g., methyl donors, vitamins and polyphenols) that have been utilized to revert or prevent the epigenetic silencing of RASSF1A. Moreover, we specify pathways that were involved in RASSF1A reactivation. Several of these compounds (e.g., reseveratol and curcumin) act by inhibiting the activity or expression of DNA methyltransferases and reactive RASSF1A in cancer. Thus natural compounds could serve as important agents in tumor prevention or cancer therapy. However, the exact epigenetic reactivation mechanism is still under investigation. View Full-Text
Keywords: DNA methylation; tumor suppressor gene; RASSF1; demethylation; natural compounds DNA methylation; tumor suppressor gene; RASSF1; demethylation; natural compounds

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Dammann, R.H.; Richter, A.M.; Jiménez, A.P.; Woods, M.; Küster, M.; Witharana, C. Impact of Natural Compounds on DNA Methylation Levels of the Tumor Suppressor Gene RASSF1A in Cancer. Int. J. Mol. Sci. 2017, 18, 2160.

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