Effects of Trehalose on Cell Growth and Maturation Correlates with Increased Expression of Mitochondrial RNA: Differentiation of HT-29 Human Colonic Adenocarcinoma Cells

The HT-29 human adenocarcinoma cell line has been used extensively in the study of colonie cell differentiation and colon cancer. We report here that substitution of glucose with trehalose (a-i>-glucopyranosyl-ai>-glucopyranoside) depresses growth and promotes mucin-producing, goblet-like maturation of HT-29. An initial characterization of this process was made by analyzing several cDNA clones whose RNA tem plates were differentially expressed at elevated levels in cells grown in trehalose-containing medium. Seven of the 9 clones examined corre sponded to 6 mitochondria! genes whose expression levels, relative to those from glucose-grown cells, ranged from approximately 3-fold for 165 rRNA to 8-23-fold for NADH dehydrogenase subunit 4. On the other hand, levels of mitochondria! DNA copy, measured by using NADH dehydrogenase subunit 4 cDNA as probe, were shown to be unaffected by trehalose treatment. Elevation of cellular NADH dehydrogenase subunit 4 RNA in HT-29 cultures grown in medium containing different components (sodium butyrate, galactose, no-sugar, glucose, cellobiose) generally correlated with depressed growth levels and specifically with increased numbers of mucin-producing cells present. Like butyrate, the sugar, trehalose, is an effective inducer of HT-29 differentiation, and may prove useful as a dietary therapeutic, and as a probe for elucidating mitochondria! involvement in colonie cell differentiation and transformation.