A 3D culture model of human HepG2 cells for evaluation of the cytotoxicity and genotoxicity of epigallocatechin-3-gallate

• Grant number: 15/14904-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2016
• End date: March 31, 2017
• Field of knowledge: Biological Sciences - Genetics - Mutagenesis
• Principal Investigator: Alexandre Ferro Aissa
• Grantee: Mariana dos Reis Simpronio
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The clinical use of antitumor drugs is usually accompanied by various side effects that compromise patients' quality of life. Therefore, the search for new antitumor agents with greater efficacy and fewer side effects has been intense. In this sense, dietary bioactive compounds such as catechins have become an interesting source in the search for these drugs. One catechin, namely epigallocatechin-3-gallate (EGCG), is the major constituent of green tea, and the beneficial biological properties of tea such antitumor, anti-Alzheimer, and anti-aging are attributed to this component. EGCG exhibits antiproliferative activity, and preliminary studies have demonstrated that this activity is associated with the induction of DNA damage in tumor cells. Currently, only in vitro systems of monolayer cell culture have been used in these studies, but such systems do not satisfactorily reflect the in vivo environment. Alternative methods that better mimic the tumor microenvironment have been proposed. One of these models includes three-dimensional (3D) cell cultures such as multicellular tumor spheroids. The 3D culture model is considered an effective method for carrying out toxicological studies. However, there is little evidence in the literature showing that the 3D cultures actually influence hepatocellular cytotoxicity and genotoxicity. Therefore, this study aims to evaluate the cytotoxic, genotoxic and oxidative potential of EGCG in human hepatocellular carcinoma cells, HepG2, grown as a 3D culture model of multicellular tumor spheroids as well as to evaluate the growth and morphology of spheroids during treatment. (AU)