Interference of various fatty acids on the DHA-related cytotoxic effect on acidosis-adapted SiHa cells

Details

Supervisors

Larondelle, Yvan ; Mignard, Louise

Faculty

Faculté des bioingénieurs

Degree label

Master [120] : bioingénieur en sciences agronomiques

Abstract

Cancer is a generic term characterizing a group of diseases involving an abnormal cell proliferation with the potential to spread and invade other parts of the body. A hallmark of solid tumours is the production of a tumour microenvironment, which in turn actively influences the tumour growth, progression and metastasis. The tumour microenvironment is defined by different gradients of hypoxia and acidosis, favored by the formation of a complex and disorganized vascular network. In these hypoxic and acidic conditions, a metabolic rewiring occurs in the cancer cells to maintain tumour growth in a particularly inhospitable cell environment. The metabolic reprogramming of these acidosis-adapted cells demonstrates an intricate dependency on fatty acids to support the cancer cell survival. Indeed, these cells show the particularity to allow the concomitance of fatty acid synthesis and oxidation, as well as the stimulation of lipid droplets formation. Fatty acids appear to play a central role in cancer cells, being source of nutrients, components of the cell membranes and precursors of signaling molecules. They can be found in the human diet under the form of saturated, monounsaturated and polyunsaturated fatty acids. Polyunsaturated fatty acids from the omega-3 family are extensively studied for their health effects in the prevention and therapy of a series of diseases, including cancer. The cytotoxic effect of docosahexaenoic acid (DHA, C22:6 n-3), has been confirmed to be specific on acidosis adapted-cancer cell lines by viability assays. However, this effect needs to be confirmed in the presence of other fatty acids. The main objective of this master thesis is the evaluation of the effect of increasing concentrations of fatty acids with different length and degree of unsaturation of their aliphatic chain on the established DHA-related cytotoxic effect at 100 μM on acidosis-adapted SiHa cells (human cervical cancer). The results demonstrated that the inhibition of the DHA-related cytotoxic effect is negatively correlated with the length and degree of unsaturation of the fatty acids. Indeed, saturated fatty acids, namely palmitic acid and stearic acid, clearly inhibited the cytotoxic effect of DHA observed on acidosis-adapted SiHa cells. A second objective is to determine if the use of a delipidated medium with 10 % charcoal-stripped fetal bovine serum (CS-FBS) during the assays is necessary to observe notable effects on the cells in comparison to a normal medium containing 10 % FBS. The cell viability assays performed in both media revealed similar effects. In addition, results from gas chromatography showed that the relatively low concentrations of fatty acids are equivalent in both media. It thus appears that the costly CS-FBS is unnecessary to appreciate the cytotoxic effects of the different fatty acids on SiHa cells. Taken together, our results open new perspectives to understand the mechanisms explaining the cytotoxicity of fatty acids on cancer cells and their possible action in physiological conditions.