Mitotic catastrophe and other cellular instability events in sodium valproate-treated HeLa cells

• Grant number: 24/00772-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2024
• End date: December 03, 2025
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Maria Luiza Silveira Mello
• Grantee: Beatriz Pierre Sforça
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

The increased incidence of mitotic catastrophe, a form of cell death that is considered to represent an onco-suppressive pathway, has been associated to depletion of DNA methyltransferase I (DNMT1), enzyme which exerts influence on the DNA methylation status. In the cervical tumorigenesis, DNMT1 affects the activity of several suppressor genes. HeLa cells, a cell line originated from cervical carcinoma, when synchronized and cultured in the presence of 1- or 20-mM sodium valproate (VPA) for 4 h, have been reported to exhibit decrease in the expression of DNMT1, and in the 5-methylcytosine level. However, only the frequency of apoptosis was found to increase, a result that occurred under the 20-mM-VPA treatment. In the present study, the effect of longer treatments with various VPA concentrations on DNMT1 expression and abundance, using Western blots and PCR, and on the frequency of mitotic catastrophes and of other nuclear instability events will be investigated using morphological features and biomarkers reported to be associated to mitotic catastrophe (caspase 2, p53). Considering that another form of DNMT (DNMT3B) that also affects DNA methylation in another type of tumor cells was recently demonstrated in our laboratory in HeLa cells, the effect of VPA on this enzyme will also be investigated. The potential benefit of VPA in inducing metabolic pathways that lead to different forms of cell death would thus be explored.