Effects of retinoic acid on expression of the transformed phenotype in C6 glioma cells.

Retinoic acid (RA) inhibited the growth and induced morphological changes in C6 rat glioma cells. The effects of RA on growth rate became apparent after 48 hr and were concentration-dependent and reversible. There was a 60% inhibition of growth using 10(-5) RA, which increased at low serum concentration to over 90% inhibition and was minimized at high concentration of serum. RA did not change the saturation density of the cells. The morphology of C6 cells, was altered from its normal pattern of randomly oriented spindle shaped cells, to cells which aligned to form palisades of fibroblast-like cells. Biochemical analysis of the cells showed no significant change in the activities of several lysosomal hydrolyses or the level of total protein in RA-treated cells compared to control cells. There was, however, a significant decrease in the activity of ornithine decarboxylase early during the treatment with RA, and an increase in the levels of fibronectin secreted into the media by the RA-treated cell. These results suggest that RA can suppress the expression of the transformed phenotype of glioma cells.