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Study of the role of Nrf2 protein in metabolism regulation and redox control in response to natural food-derived compounds in Prostate Cancer cells

Grant number: 19/25582-9
Support type:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): March 01, 2020
Effective date (End): February 29, 2024
Field of knowledge:Health Sciences - Nutrition
Principal Investigator:Fernando Moreira Simabuco
Grantee:Mariana Camargo Silva Mancini
Home Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil
Associated research grant:18/14818-9 - Study of molecular targets important for the control of cancer metabolism: the mTOR/S6K pathway as a central role, AP.JP2

Abstract

Nrf2 (Nuclear factor erythroid 2-related factor 2) protein is considered one of the major regulators of oxidative stress and, once activated, triggers important changes in the expression of several genes involved in redox homeostasis, drug and cell metabolism, survival, proliferation, autophagy, proteasome degradation, DNA repair and mitochondrial biology. Several studies describe a preventive role of Nrf2 in Cancer, while others have characterized that Nrf2 activation can promote Cancer progression, metastasis, and resistance to chemotherapy and radiotherapy. Nrf2 also plays a dual role in the mTOR pathway, turning activated or inhibited by rapamycin, which may reflect its ambiguous role in Cancer. On the other hand, it has been shown that Nrf2 can activate the mTOR pathway, showing a complex relationship between these two important proteins. Several natural food-derived compounds, including phenolic compounds, have been exploited for their ability to prevent or inhibit Cancer cells by modulating the Nrf2 pathway. This project aims to study the relationship between Nrf2 and mTOR pathway in response to phenolic compounds derived from food extracts. Through modulation of Nrf2 expression, by overexpression or CRISPR/Cas9-mediated knockout, we will evaluate how Prostate Cancer cells respond to extracts of food and compounds such as betanin and vitexin, extracted from beet. In addition, Nrf2 modulation can impact metabolic changes in Cancer cells mediated by mTOR signaling and also changes in the redox control. This project may contribute to a better understanding of the role of Nrf2 in Cancer progression and its relationship with the mTOR/S6Ks pathway. (AU)