Dl-alpha-tocopherol,a potent inhibitor of phorbol ester induced shape change of erythro- and megakaryoblastic leukemia cells

Synthetic vitamin E, dl-α-tocopherol, added to a human erythroleukemia HEL and a megakaryoblastic leukemia, Meg-01, cell culture produced potent dose-dependent inhibition of phorbol ester-induced adhesion and of the morphologic changes accompanying it. The inhibition was reversible by withdrawal of supplemental vitamin E from the medium. dl-α-Tocopherol also inhibited protein kinase C activity both at baseline and after phorbol ester stimulation. Arachidonic acid stimulated protein kinase C activity of erythroleukemia cells and promoted their adhesion, an effect that was also inhibited by dl-α-tocopherol. Introduction of a protein kinase C-neutralizing antibody or a protein kinase C-inhibitor substrate into permeabilized HEL cells inhibited phorbol ester-induced adhesion and shape change. dl-α-Tocopherol also affected the cellular distribution of protein kinase C, shifting the major portion of the enzyme to the cytosol fraction and reducing phorbol ester-induced membrane association of the enzyme. Thus, protein kinase C appears to mediate shape change and adhesion, both of which are strongly inhibited by dl-α-tocopherol. J. Cell. Physiol. 172:351–360, 1997. © 1997 Wiley-Liss, Inc.