Effects of fatty acids on expression of genes encoding subunits of cytochrome c oxidase and cytochrome c oxidase activity in HT29 human colonic adenocarcinoma cells.

As the primary and preferred energy source of normal colonic epithelial cells, fatty acids may play a unique role in the differentiation and physiology of these cells. We have shown that expression levels of COXIII, a mitochondrial gene encoding one of the 13 subunits of cytochrome c oxidase, are abnormally low in colon tumors and colonic tissue at genetic risk for developing tumors but increase following in vitro treatment of HT29 human colonic adenocarcinoma cells with the fatty acid butyrate. The present studies investigate the specificity of fatty acids in effecting cytochrome c oxidase subunit expression and enzymatic activity in HT29 cells. The data demonstrate that, depending upon their chain length, metabolizable unbranched fatty acids increase expression of two subunits encoded by mitochondrial genes (I and III) and enhance cytochrome c oxidase activity. However, none of the fatty acids had an effect on expression of two subunits encoded by nuclear genes (IV and Va). These findings suggest that the low levels of COXIII expression exhibited in colonic tumors may represent a limiting factor in the assembly of functional cytochrome c oxidase and contribute to the depressed enzyme activity reported in these tumors. By elevating expression of subunits I and III and enzymatic activity, fatty acids may enhance the potential for cellular respiration. The more differentiated phenotype which is reported in colorectal carcinoma cell lines treated with fatty acids in vitro may be, therefore, associated with correction of metabolic abnormalities in transformed cells.