GROWTH-INHIBITION AND APOPTOSIS OF RL HUMAN B-LYMPHOMA-CELLS BY VITAMIN-E SUCCINATE AND RETINOIC ACID - ROLE FOR TRANSFORMING GROWTH-FACTOR-BETA

Vitamin E succinate (VES) and all-trans-retinoic acid (RA) were determ ined to be growth inhibitory for B lymphoma cells in vitro. RL, an Eps tein-Barr virus-negative human cell line, was growth suppressed 87% wi th VES (5 mu g/ml) and 58% with RA (10(-6)M); both agents blocked the cells in G(1) of the cell cycle. The antiproliferative effect of VES s eems to be independent of its potential antioxidant property because b oth fat- and water-soluble antioxidants were found to have no effect o n pL cell proliferation. VES and RA increased IgM antibody concentrati ons in cell supernatants 5.8- and 9.9-fold, respectively. DNA fragment ation and flow cytometry studies showed VES- and RA-induced apoptosis in RL cells. VES- and RA-treated RL cells gradually underwent apoptosi s over time with maximal induction occurring at days 6 and 5 of cultur e, respectively. A role for transforming growth factor beta in VES- an d RA-mediated RL growth suppression is indicated by increased ligand a nd type II receptor protein expression. Furthermore, neutralizing anti bodies to transforming growth factor beta 1 partially blocked the grow th suppressive action of both VES and RA, thus suggesting that a TCF-b eta autocrine negative loop was involved in VES and RA suppression of RL cell growth.