Study of the mechanisms of action of gamma-linolenic acid in C6 rat glioma cells

• Grant number: 06/01481-9
• Support Opportunities: Regular Research Grants
• Start date: December 01, 2006
• End date: July 31, 2009
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Alison Colquhoun
• Grantee: Alison Colquhoun
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Gamma-linolenic acid (GLA) is an inhibitor of proliferation and migration in the C6 rat glioma cell line. GLA and the n-3 polyunsaturated fatty acids eicosapentaneoic and docosahexaenoic acid can influence several aspects of cell proliferation and cell death as well as interfering with the processes of cell migration and invasion. Despite the existence of these findings in the literature, the mechanisms of action of these polyunsaturated fatty acids are still poorly understood and their comprehension will be the main objective of the present study. GLA will be the fatty acid of choice as it has been used in the treatment of patients with terminal stage gliomas with some success. The project aims to provide a clearer understanding of the pathways by which GLA interferes with glioma progression. The main points of interest will be the control of the cell cycle, apoptosis, cell migration and invasion, eicosanoid metabolism and angiogenesis. The effects of GLA upon mRNA and protein expression of proteins of particular importance in gliomas will be analysed. The effects of GLA upon tumour morphology and vascular organisation and vascular density will be determined. The final aspect which will be studied is the activation of intracellular signalling pathways most important to glioma biology, with the intention of identifying whether or not GLA acts through these or other signalling pathways. It is hoped that using this approach to the problem will provide valuable information regarding the mechanisms of action of GLA in gliomas both in vitro and in vivo. (AU)