THE EFFECT OF ALPHA-TOCOPHEROL AND BETA-TOCOPHEROL ON PROLIFERATION, PROTEIN-KINASE-C ACTIVITY AND GENE-EXPRESSION IN DIFFERENT CELL-LINES

alpha-Tocopherol, but not beta-tocopherol, negatively regulates prolif eration of A7r5 vascular smooth muscle cells at physiological concentr ation. The HeLa cell line was not affected whereas the Chinese hamster ovary cell line (CHO) was slightly inhibited by both alpha-tocopherol and beta-tocopherol. In A7r5 cells a-tocopherol inhibited protein kin ase C activity, and this correlated with inhibition of proliferation. beta-Tocopherol did not inhibit either protein kinase C or proliferati on. In HeLa cells no inhibition by alpha-tocopherol or beta-tocopherol of protein kinase C activity and cell proliferation was observed. In Chinese hamster ovary cells both tocopherols inhibited protein kinase C activity but not proliferation. Thus in the latter cells proliferati on was not protein kinase C-dependent. In A7r5 cells alpha-tocopherol but not beta-tocopherol activated AP-1-mediated gene expression. In He La cells no change in gene expression was observed in agreement with t he finding that also protein kinase C was not affected. In CHO cells g ene expression was activated by both alpha-tocopherol and beta-tocophe rol. In this case also a positive correlation was found with similar i nhibition of protein kinase C activity. In these cells, however, the c hanges at the level of protein kinase C activity and gene expression d id not result in proliferation changes. The effect of alpha-tocopherol and beta-tocopherol on protein kinase C activity and gene expression suggest a cause-to-effect relationship. Inhibition of proliferation, h owever, correlates in the case of A7r5 and HeLa cells but not in the c ase of CHO suggesting a different proliferation pathway for these cell s.