Effect of docosahexaenoic acid (DHA) on epigenetic events involved in different breast cancer cell lines

• Grant number: 10/19706-2
• Support Opportunities: Regular Research Grants
• Start date: April 01, 2011
• End date: March 31, 2013
• Field of knowledge: Health Sciences - Nutrition - Nutrition Biochemistry
• Principal Investigator: Dan Linetzky Waitzberg
• Grantee: Dan Linetzky Waitzberg
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Maria Mitzi Brentani

Abstract

Epigenetic changes, such as DNA methylation and post-translational modifications of histones has an important role in mammary tumorigenesis. Changes in DNA methylation are the most studied, which include global hypomethylation and hypermethylation of promoter regions of specific genes. Several genes are hypermethylated in breast cancer, especially the tumor suppressor gene RASSF1A, for their potential prognostic value. Epigenetic events are important as therapeutic targets due to its reversible character. Dietary compounds can modulate the epigenetic processes in cancer. Experimentally, docosahexaenoic acid (DHA), a member of the omega-3 fatty acids, can reduce proliferation, induce apoptosis and decrease the invasive potential of breast tumor cells. Moreover, this fatty acid promotes reactivation of genes silenced by hypermethylation in promoter region and is involved in epigenetic events through post-translational modifications of histones. However, the antitumor mechanisms of DHA and its ability to modulate epigenetic events are not yet fully elucidated. Our aim is to verify the in vitro action of DHA in epigenetic events of reactivation of RASSF1A gene in different human breast cancer cell lines. (AU)