Influence of sulforaphane, an inhibitor of histone deacetylases on the genomic instability and epigenetic mechanisms in human cell lines

• Grant number: 16/14703-1
• Support Opportunities: Scholarships in Brazil - Master
• Start date: April 01, 2017
• End date: November 30, 2018
• Field of knowledge: Health Sciences - Nutrition - Nutrition Biochemistry
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Lusânia Maria Greggi Antunes
• Grantee: Patrick Wellington da Silva dos Santos
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated scholarship(s): 17/21561-1 - Effects of sulforaphane on DNA methylation patterns and transcriptome analysis in cancer and non-cancer cells, BE.EP.MS

Abstract

Underlying the hallmarks of cancer are genomic instability and epigenetic mechanisms that influence the expression of genes related to the maintenance of genomic stability. Among the epigenetic mechanisms, DNA methylation is the most studied and relevant. Cancer incidence depends on interactions between genome and epigenome that together interact with environmental factors including diet. The potential diet importance in cancer prevention is widely known due to a considerable amount of evidence from basic, epidemiological and clinical research. Bioactive dietary compounds have shown as potential chemopreventive through their influence in the maintenance of genomic stability and epigenetic mechanisms. A promising bioactive compound is the sulforaphane, found in high concentrations in cruciferous vegetables - Brassicaceae family. It has been shown that sulforaphane can activates genes silenced by DNA hypermethylation in tumor cells. However, there is limited information on the influence of sulforaphane on methylation pattern in the promoter region of tumor suppressor genes and oncogenes. Therefore, the aim of this research project is to evaluate the sulforaphane ability to influence differentially genomic instability (by comet assay and micronucleus) and epigenetic mechanisms by changes in methylation pattern of gene promoter region of tumor suppressor genes SFRP1 and RASSF1 and oncogenes MUC1 and MET (by MS-HRM) and correlate the methylation pattern of these genes with expression, as evaluated by RT-qPCR on gastric cells and human hepatocellular carcinoma cells (HepG2. (AU)

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)

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)

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)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

SANTOS, Patrick Wellington da Silva dos. Influence of sulforaphane, an inhibitor of histone deacetylases on the genomic instability and epigenetic mechanisms in human cell lines. 2019. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Ciências Farmacêuticas de Ribeirão Preto (PCARP/BC) Ribeirão Preto.