Metabolic effects of 3-thia fatty acid in cancer cells.

Abstract

Gliomas are tumours of glial cell origin in the central nervous system (CNS). High grade malignant gliomas are very aggressive and almost always lethal. Although the treatment of neoplasms in other organ systems has radically improved during the last decade, improvements in glioma treatment have been marginal. Combinations of surgery, radiotherapy and chemotherapy may gain some weeks or months in survival time, however the median survival time after treatment is less than a year. The aggressiveness of cancers depends on qualities such as proliferative rate, invasiveness and angiogenesis. Agents that influence one or more of these features may affect the tumour malignancy. Characteristic for the neuroepithelial tumours is their local invasive behavior. Neuroepithelial tumours are poorly demarcated and hardly ever properly encapsulated. This behavior makes complete surgical removal of the tumour difficult and they often recur with a fatal result. It is largely accepted that a high dietary intake of poly-unsaturated fatty acids (PUFA) in the series has beneficial effects. Recently, cellular lipid metabolism has been suggested as a target for cancer therapy. Cancer cells, compared with normal cells, seem to be vulnerable to exposure of certain polyunsaturated fatty acids (PUFAs), especially those in the series. Characteristic for these compounds are their poor ability to be oxidized in the cell due to multiple double bonds. They are however likely to be esterified to other lipids, and their incorporation into membrane phospholipids will influence membrane properties such as fluidity, protein interactions and susceptibility to lipid peroxidation. The hypolipidemic properties of some fatty acids, such as EPA, are probably explained by an induction of mitochondrial β -oxidation3 that is not found after administration of the non-hypolipidemic PUFA docosahexaenoic acid (DHA). However, both eicosapentaenoic acid (EPA) and DHA cause increased peroxisomal