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Toxicological evaluation of diallyl disulfide associated with the chemotherapeutic agent sorafenib: investigation of cell death and expression of proteins in human liver cells in vitro

Grant number: 19/08348-2
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): September 01, 2019
Effective date (End): June 30, 2021
Field of knowledge:Health Sciences - Pharmacy - Toxicological Analysis
Principal Investigator:Lusânia Maria Greggi Antunes
Grantee:Ana Rita Thomazela Machado
Home Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Hepatocellular Carcinoma is one of the most common Cancers in adults. Sorafenib is the only drug available in the clinic in advanced stages, but many patients exhibit tumor progression during chemotherapy, which leads to the search for new treatments. The occurrence of the disease may be reduced and/or its development controlled by synergistic mechanisms in combination with diet bioactive compounds and drugs. Since much evidence suggests bioactive diet compounds as promising in the treatment of Cancer, such as diallyl disulfide, a garlic organosulforated compound that exerts antitumor activity on certain Cancers types. Thus, the aim of this study is to evaluate the effects of diallyl disulfide isolated and associated with the chemotherapy sorafenib, on the response in Hepatocellular Carcinoma (HepG2) cells. We will investigate cytotoxicity and cell viability, cell death by apoptosis and autophagy, cell migration and invasion, genotoxicity and expression of proteins related to resistance to cell death (BAX and BCL2), cell invasion and migration (CTNNB1, MMP2 and CDH1 ), the inactivation of tumor suppressors (MYC) and cell proliferation (RELA) by western blot. This project also pretend to contribute for the identification of an initial molecular event related to cell death in HepG2 cells treated with diallyl disulfide. This is in according to the Adverse Outcome Pathway (AOP) once cell death is one of the major events proposed for AOP to make Hepatocellular Carcinoma. (AU)