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 Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: March 01, 2020
• End date: April 30, 2025
• Field of knowledge: Health Sciences - Nutrition - Nutrition Biochemistry
• Principal Investigator: Fernando Moreira Simabuco
• Grantee: Mariana Camargo Silva Mancini
• Host 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
• Associated scholarship(s): 22/10223-6 - Characterization of the relationship between NRF2 and the mTOR/S6Ks pathway using genetically engineered mouse models (GEMMs), BE.EP.DD

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)

Scientific publications

(6)

(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)

SILVA MANCINI, MARIANA CAMARGO; SABOIA PONTE, LUIS GUSTAVO; ROCHA SILVA, CAYO HENRIQUE; FAGUNDES, ISABELLA; BETIM PAVAN, ISADORA CAROLINA; ROMEIRO, STEFHANI ANDRIOLI; SALVINO DA SILVA, LUIZ GUILHERME; MORELLI, ANA PAULA; ROSTAGNO, MAURICIO ARIEL; SIMABUCO, FERNANDO MOREIRA; et al. Beetroot and leaf extracts present protective effects against prostate cancer cells, inhibiting cell proliferation, migration, and growth signaling pathways. Phytotherapy Research, JUN 2021. (18/14818-9, 16/06457-0, 19/25582-9, 15/00311-1, 19/00607-9, 19/13848-4)

ROMERO, STEFHANI ANDRIOLI; BETIM PAVAN, ISADORA CAROLINA; MORELLI, ANA PAULA; SILVA MANCINI, MARIANA CAMARGO; SALVINO DA SILVA, LUIZ GUILHERME; FAGUNDES, ISABELLA; ROCHA SILVA, CAYO HENRIQUE; SABOIA PONTE, LUIS GUSTAVO; ROSTAGNO, MAURICIO ARIEL; NEVES BEZERRA, ROSANGELA MARIA; et al. Anticancer effects of root and beet leaf extracts (Beta vulgaris L.) in cervical cancer cells (HeLa). Phytotherapy Research, v. 35, n. 11, SEP 2021. (18/14818-9, 16/06457-0, 19/25582-9, 15/00311-1, 19/00607-9, 19/13848-4)

PONTE, LUIS GUSTAVO SABOIA; PAVAN, ISADORA CAROLINA BETIM; MANCINI, MARIANA CAMARGO SILVA; DA SILVA, LUIZ GUILHERME SALVINO; MORELLI, ANA PAULA; SEVERINO, MATHEUS BRANDEMARTE; BEZERRA, ROSANGELA MARIA NEVES; SIMABUCO, FERNANDO MOREIRA. The Hallmarks of Flavonoids in Cancer. Molecules, v. 26, n. 7, APR 2021. (18/08391-2, 19/00607-9, 19/25582-9, 18/14818-9)

MORELLI, ANA PAULA; TORTELLI JR, THARCISIO CITRANGULO; SILVA MANCINI, MARIANA CAMARGO; BETIM PAVAN, ISADORA CAROLINA; SALVINO SILVA, LUIZ GUILHERME; SEVERINO, MATHEUS BRANDEMARTE; GRANATO, DANIELA CAMPOS; PESTANA, NATHALIE FORTES; SABOIA PONTE, LUIS GUSTAVO; PERUCA, GUILHERME FRANCISCO; et al. TAT3 contributes to cisplatin resistance, modulating EMT markers, and the mTOR signaling in lung adenocarcinom. Neoplasia, v. 23, n. 10, p. 1048-1058, OCT 2021. (19/25582-9, 15/22814-5, 15/00311-1, 18/14818-9, 19/00607-9, 20/09527-5)

MANCINI, MARIANA C. S.; MORELLI, ANA P.; SEVERINO, MATHEUS B.; PAVAN, ISADORA C. B.; ZAMBALDE, ERIKA P.; GOIS, MARIANA M.; DA SILVA, LUIZ G. S.; QUINTERO-RUIZ, NATHALIA; ROMEIRO, CAIO F.; DOS SANTOS JR, DANIEL F. G.; et al. Knockout of NRF2 triggers prostate cancer cells death through ROS modulation and sensitizes to cisplatin. Journal of Cellular Biochemistry, v. 123, n. 12, p. 14-pg., 2022-10-03. (20/09310-6, 20/09133-7, 16/06457-0, 20/13660-2, 20/09527-5, 15/00311-1, 20/08684-0, 18/14818-9, 19/00607-9, 19/25582-9, 19/25731-4)

SILVA MANCINI, MARIANA CAMARGO; SABOIA PONTE, LUIS GUSTAVO; ROCHA SILVA, CAYO HENRIQUE; FAGUNDES, ISABELLA; BETIM PAVAN, ISADORA CAROLINA; ROMEIRO, STEFHANI ANDRIOLI; SALVINO DA SILVA, LUIZ GUILHERME; MORELLI, ANA PAULA; ROSTAGNO, MAURICIO ARIEL; SIMABUCO, FERNANDO MOREIRA; et al. Beetroot and leaf extracts present protective effects against prostate cancer cells, inhibiting cell proliferation, migration, and growth signaling pathways. Phytotherapy Research, v. 35, n. 9, p. 5241-5258, SEP 2021. (19/13848-4, 18/14818-9, 16/06457-0, 15/00311-1, 19/25582-9, 19/00607-9)