Role of norepinephrine on oral cancer behavior and chemoresistance: epigenetic changes and cancer stem cell maintenance

• Grant number: 17/24685-3
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: March 31, 2018
• End date: March 30, 2019
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Sandra Helena Penha de Oliveira
• Grantee: Kellen Cristine Tjioe
• Supervisor: Rogerio Moraes Castilho
• Host Institution: Faculdade de Odontologia (FOA). Universidade Estadual Paulista (UNESP). Campus de Araçatuba. Araçatuba , SP, Brazil
• Institution abroad: University of Michigan, United States
• Associated to the scholarship: 16/00051-2 - Influence of distress hormones on the oral cancer cells resistance to chemotherapy, BP.PD

Abstract

Recent studies demonstrate that the stress hormone norepinephrine (NE) exerts a pivotal role in the progression and in the chemoresistance of different types of cancer but its epigenetic mechanisms remain poorly understood. Moreover, the participation of cancer stem cells (CSC) in such processes is also a mystery. In fact, those questions have not been addressed in head and neck squamous cell carcinoma (HNSCC) yet. Thus, our aim is to investigate if histones acetylation statuses and cancer stem cells maintenance regulate the mechanisms and chemoresistance induced by norepinephrine in HNSCC cells. HNSCC cell lines SCC-9, SCC-15, HN6, HN12, and HN13 will be stimulated with NE for 1 hour following treatment with the inhibitory concentration 50 of cisplatin. Histones acetylation status, histone deacetylases, epithelial-mesenchyme transition, CSC, and chemoresistance-associated proteins expression will be verified by western blotting and immunofluorescence. CSCs will be characterized and quantified by the enzymatic activity of aldehyde dehydrogenase (ALDH), CD44, or CD133, and Hoeschst 33342 exclusion assays by flow cytometry. Tumorsphere formation assay will be used as a biological readout of the treatment. All the experiments will be performed in triplicate and, at least, 3 independent times. Data will be statistically analyzed according to the normality test and p levels below 0.05 will be considered significant. (AU)