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

Autor: Michelle L. Woods, Miriam M. Küster, Antje M. Richter, Adriana P. Jiménez, Reinhard Dammann, Chamindri Witharana
Rok vydání: 2017
Předmět:
0301 basic medicine
endocrine system
Methyltransferase
Tumor suppressor gene
Review
Cytidine
Biology
medicine.disease_cause
Catalysis
Epigenesis
Genetic
lcsh:Chemistry
Inorganic Chemistry
03 medical and health sciences
0302 clinical medicine
Neoplasms
natural compounds
medicine
Animals
Humans
Genes
Tumor Suppressor
Cancer epigenetics
Epigenetics
tumor suppressor gene
Physical and Theoretical Chemistry
lcsh:QH301-705.5
Molecular Biology
Spectroscopy
Biological Products
DNA methylation
Tumor Suppressor Proteins
Organic Chemistry
demethylation
Polyphenols
Cancer
Vitamins
General Medicine
medicine.disease
Molecular biology
Computer Science Applications
Gene Expression Regulation
Neoplastic
030104 developmental biology
lcsh:Biology (General)
lcsh:QD1-999
Tumor progression
030220 oncology & carcinogenesis
Cancer research
RASSF1
Carcinogenesis
Zdroj: International Journal of Molecular Sciences
International Journal of Molecular Sciences, Vol 18, Iss 10, p 2160 (2017)
ISSN: 1422-0067
DOI: 10.3390/ijms18102160
Popis: 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.
Databáze: OpenAIRE
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