Effects of sulforaphane on DNA methylation patterns and transcriptome analysis in cancer and non-cancer cells

• Grant number: 17/21561-1
• Support Opportunities: Scholarships abroad - Research Internship - Master's degree
• Start date: February 01, 2018
• End date: July 31, 2018
• Field of knowledge: Health Sciences - Nutrition - Nutrition Biochemistry
• Principal Investigator: Lusânia Maria Greggi Antunes
• Grantee: Patrick Wellington da Silva dos Santos
• Supervisor: Matteo Pellegrini
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: University of California, Los Angeles (UCLA), United States
• Associated to the scholarship: 16/14703-1 - Influence of sulforaphane, an inhibitor of histone deacetylases on the genomic instability and epigenetic mechanisms in human cell lines, BP.MS

Abstract

Cancer is a growing problem for human health worldwide. The occurrence of cancer is related to population aging, as well as the prevalence of risk factors. Epigenetic and genetic alterations contribute to cancer initiation and progression. Epigenetics is a non-Mendelian inheritance of DNA modifications, which, do not affect the DNA base sequence, but may influence the expression of genes. Several studies suggest that a number of dietary compounds play a major role as epigenetic modulators against the initiation and the progression of several types of cancer. Sulforaphane, a natural isothiocyanate from cruciferous vegetables, is a well-known histone deacetylases inhibitor. However, the influence of sulforaphane in DNA methylation and chromatin condensation status is not fully clear. New methods and progress have been made in order to identify generally silenced genes, and mRNA expression changes. Therefore, the aim of this study is to analyze the overall DNA methylation profile of cancer and non-cancer cells after treatment of sulforaphane using high-throughput technologies. In order to find regions of interest that are epigenetically modulated by sulforaphane, the RRBS (reduced representation bisulfite sequencing) will be performed. Moreover, to determine gene expression dynamics and transcriptome changes in cancer and non-cancer cells after treatment of sulforaphane by RNA-seq. Finally, to investigate the influence of sulforaphane with proteins related to chromatin condensation by chromatin-immunoprecipitation followed by a high-throughput DNA sequencing (ChIP-Seq). These studies will provide valuable and actionable information about the genome-wide influence of sulforaphane and may add relevance of sulforaphane promising cancer prevention agent.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SANTOS, PATRICK WELLINGTON; THOMAZELA MACHADO, ANA RITA; DE GRANDIS, RONE; RIBEIRO, DIEGO LUIS; TUTTIS, KATIUSKA; MORSELLI, MARCO; AISSA, ALEXANDRE FERRO; PELLEGRINI, MATTEO; GREGGI ANTUNES, LUSANIA MARIA. Effects of sulforaphane on the oxidative response, apoptosis, and the transcriptional profile of human stomach mucosa cells in vitro. MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS, v. 854, JUN-JUL 2020. (16/14703-1, 17/21561-1, 17/24576-0)

DA SILVA DOS SANTOS, PATRICK WELLINGTON; THOMAZELA MACHADO, ANA RITA; DE GRANDIS, RONE APARECIDO; RIBEIRO, DIEGO LUIS; TUTTIS, KATIUSKA; MORSELLI, MARCO; AISSA, ALEXANDRE FERRO; PELLEGRINI, MATTEO; GREGGI ANTUNES, LUSANIA MARIA. Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food and Chemical Toxicology, v. 136, FEB 2020. (16/14703-1, 17/21561-1, 17/24576-0)