Regulation of cellular differentiation and apoptosis by fatty acids and their metabolites.
We have reviewed the literature regarding the effects of fatty acids and their metabolites on cellular differentiation and apoptosis. Results obtained in different studies have been variable, but some generalizations can be made. Differentiation was increased by incubation of cells with arachidonic acid (AA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), prostaglandin E1 (PGE1), prostaglandin E2 (PGE2), or leukotriene D4 (LTD4). Effects of these agents on differentiation could be magnified with the simultaneous addition of other differentiation-inducing agents like dimethylsulfoxide or retinoic acid. AA and gamma-linolenic acid increased apoptosis while the effects of n-3 fatty acids (EPA and DHA) and of eicosanoids varied from stimulation to inhibition. These inconsistencies are attributed to the differences in methods used to evaluate differentiation and apoptosis, concentrations of fatty acids and serum, exposure time and the cell models used. Studies using the physiological concentrations of the fatty acids and standardized experimental conditions need to be conducted to establish effects of fatty acids and their metabolites on these cellular processes.