dl-alpha-tocopherol, a potent inhibitor of phorbol ester induced shape change of erythro- and megakaryoblastic leukemia cells.
Synthetic vitamin E, dl-alpha-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-alpha-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-alpha-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-alpha-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-alpha-tocopherol.
Steiner
M
M
Division of Hematology/Oncology, East Carolina University School of Medicine, Greenville, NC 27858-4354, USA.
Li
W
W
Ciaramella
J M
JM
Anagnostou
A
A
Sigounas
G
G
D016718:Arachidonic Acid / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002462:Cell Membrane / Q000201:enzymology; D048429:Cell Size / Q000187:drug effects*; D003600:Cytosol / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000201:enzymology / Q000473:pathology*; D007947:Leukemia, Megakaryoblastic, Acute / Q000201:enzymology / Q000473:pathology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011554:Pseudopodia / Q000187:drug effects / Q000648:ultrastructure; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors*; D014407:Tumor Cells, Cultured; D014810:Vitamin E / Q000494:pharmacology*
D014810:Vitamin E; D016718:Arachidonic Acid; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate