Mechanistic investigation of sulforaphane effects on the stemness phenotype of triple-negative breast cancer cells

• Grant number: 21/14642-0
• Support Opportunities: Scholarships abroad - Research Internship - Master's degree
• Start date: March 15, 2022
• End date: September 14, 2022
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Maria Cristina Rodrigues Rangel
• Grantee: Leandro de Lima Coutinho
• Supervisor: David Anderson Wink
• Host Institution: Instituto do Câncer do Estado de São Paulo Octavio Frias de Oliveira (ICESP). Coordenadoria de Serviços de Saúde (CSS). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Institution abroad: National Cancer Institute (NCI), Frederick, United States
• Associated to the scholarship: 20/04007-3 - Sensitization of triple-negative breast cancer to chemotherapy by the inhibition cancer stem cells self-renewal, BP.MS

Abstract

Triple-negative Breast Cancer (TNBC) refers to a cluster of highly heterogeneous diseases that lack hormonal (progesterone and estrogen) receptors, as well as HER2 protein expression/amplification. In addition, this molecular breast cancer subtype has a considerable amount of a functionally heterogeneous subpopulation of cells capable of self-renewal, differentiate and initiate tumors. These cells are termed Cancer Stem Cells (CSCs) and studies have shown that they are involved in therapy resistance acquisition. One of the signaling pathways found to be dysregulated in CSCs is the Cripto-1/NODAL pathway responsible for maintaining the stem-like phenotype of these cells. Also, studies have shown that Nitric Oxide (NO) is able to induce stem-like properties in some cancers, including TNBC. Thus, modulating NO levels may impact the CSC population and it may help to reverse and/or avoid the development of stemness features. In this regard, sulforaphane (SFN), a natural isothiocyanate compound mainly found in cruciferous vegetables, e.g. broccoli and cauliflower, has been shown to impact NO synthesis and consequently its serum levels in some pathological situations, such as H. pylori infection. Therefore, the aim of the present study is to investigate possible NO-dependent mechanisms involved in SFN effects in the TNBC CSCs population. (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)

COUTINHO, LEANDRO DE LIMA; TORTELLI JUNIOR, THARCISIO CITRANGULO; RANGEL, MARIA CRISTINA. Sulforaphane: An emergent anti-cancer stem cell agent. FRONTIERS IN ONCOLOGY, v. 13, p. 10-pg., 2023-01-23. (18/08107-2, 21/14642-0, 20/04007-3)

CHENG, ROBERT Y. S.; RIDNOUR, LISA A.; WINK, ADELAIDE L.; GONZALEZ, ANA L.; FEMINO, ELISE L.; RITTSCHER, HELENE; SOMASUNDARAM, VEENA; HEINZ, WILLIAM F.; COUTINHO, LEANDRO; RANGEL, M. CRISTINA; et al. Interferon-gamma is quintessential for NOS2 and COX2 expression in ER- breast tumors that lead to poor outcome. CELL DEATH & DISEASE, v. 14, n. 5, p. 12-pg., 2023-05-11. (18/08107-2, 21/14642-0)