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Dl‐alpha‐tocopherol, a potent inhibitor of phorbol ester induced shape change of erythro‐ and megakaryoblastic leukemia cells
Author(s) -
Steiner Manfred,
Li Wei,
Ciaramella Jason M.,
Anagnostou Athanasius,
Sigounas George
Publication year - 1997
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/(sici)1097-4652(199709)172:3<351::aid-jcp9>3.0.co;2-n
Subject(s) - protein kinase c , biochemistry , protein kinase a , phorbol , arachidonic acid , kinase , microbiology and biotechnology , chemistry , biology , enzyme
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.