The epigenetic mechanisms of gene expression control participate in the cellular response to environmental signals of biotic and abiotic nature, which reflects in the processes of cell differentiation, development of genetic and infectious diseases. The identification and analysis of these mechanisms have allowed for the development of "epigenetic drugs" to fight cancer and is exemplified by the DNA methylation inhibitor 5-azacytidine. DNA methylation is also involved in the process of infection by viruses and bacteria, which indicate the exploitation of epigenetic drugs to combat infections too. In this sense, natural products are a rich source of possibilities to increase the arsenal of "epigenetic drugs" and could have lower cytotoxic and genotoxic effects. This study aims to analyze the effect of natural products and DNA methyltransferases inhibitors in the vitro infection of canine cells by Ehrlichia canis, the etiologic agent of canine monocytic ehrlichiosis (CME), in the DNA methylation landscape of canine tumor cells and expression of genes coding DNA methyltransferases. Substances from the class of flavonoids, marine natural products and synthetic inhibitors of DNA methylation will be tested. The knowledge of the biological effects of these substances can pinpoint targets for the development of epigenetic drugs, with a positive impact for the treatment of canine cancer and EMC, diseases with high incidence in dogs.
News published in Agência FAPESP Newsletter about the scholarship: