A combination of punicic acid and docosahexaenoic acid as cytotoxic agent to cancer cells grown at physiological pH or under chronic acidosis

Details

Supervisors

Larondelle, Yvan

Faculty

Faculté des bioingénieurs

Degree label

Master [120] : bioingénieur en chimie et bioindustries

Abstract

Cancer is the second leading cause of mortality worldwide. In Belgium, one in four adults will be diagnosed with cancer before the age of 75. A third of all cancer-associated deaths is due to behavioural and dietary risks like the lack of physical activity and an unhealthy diet. Cancer accounts for a large group of diseases that occur when abnormal cells grow in an uncontrolled manner, invade neighbouring tissues and spread through the body. Throughout tumour development, cancer cells can face different conditions in their microenvironment that may trigger some metabolic adaptations in order for the cells to survive and proliferate. In particular, acidosis has been shown to induce a shift in cancer cell metabolism from glucose toward glutamine and exogenous fatty acids. While fatty acid oxidation and fatty acid synthesis are two mutually exclusive pathways in normal cells, both can take place simultaneously in cancer cells under chronic acidosis, these cells becoming reliant on exogenous fatty acids. Among them, docosahexaenoic acid (DHA, C22:6 all-cis 4,7,10,13,16,19) and conjugated linolenic acids (CLnAs) such as punicic acid (PunA, C18:3c9t11c13) or alpha-eleostearic acid (C18:3c9t11t13) have been shown to be particularly cytotoxic for cancer cells. PunA and DHA cytotoxicities have been studied in vitro on SiHa, FaDu and HCT116 cancer cell lines (cervix, pharyngeal and colon cancer) grown in physiologically-neutral conditions (pH 7.4) or under chronic acidosis (pH 6.5). The results obtained are kept confidential.