Inhibition of cell proliferation by alpha-tocopherol. Role of protein kinase C

• Published in: The Journal of biological chemistry 1991-04, Vol.266 (10), p.6188-6194
• Main Authors: Boscoboinik, D, Szewczyk, A, Hensey, C, Azzi, A
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Blotting, Western; Butylated Hydroxytoluene - pharmacology; Cell Fractionation; Cell physiology; cell proliferation; Cells, Cultured; Chromans - pharmacology; Digitonin - pharmacology; DNA - analysis; fibroblasts; Fundamental and applied biological sciences. Psychology; Mice; Molecular and cellular biology; Muscle Development; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - growth & development; neuroblastoma cells; osteosarcoma; Phorbol Esters - pharmacology; Phosphorylation; protein kinase C; Protein Kinase C - antagonists & inhibitors; Protein Kinase C - metabolism; Protein Kinase C - physiology; Rats; Responses to growth factors, tumor promotors, other factors; Vitamin E - pharmacology
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(18)38102-X

The effect of alpha-tocopherol (vitamin E) on the proliferation of vascular smooth muscle cells (A7r5), human osteosarcoma cells (Saos-2), fibroblasts (Balb/3T3), and neuroblastoma cells (NB2A) has been studied. The proliferation of vascular smooth muscle cells was inhibited by physiologically relevant concentrations of alpha-tocopherol, neuroblastoma cells were only sensitive to higher alpha-tocopherol concentrations, and proliferation of the other cell lines was not inhibited. The inhibition of smooth muscle cell proliferation was specific for alpha-tocopherol. Trolox, phytol, and alpha-tocopherol esters had no effect. Proliferation of smooth muscle cells stimulated by platelet-derived growth factor or endothelin was completely sensitive to alpha-tocopherol. If smooth muscle cells were stimulated by fetal calf serum, proliferation was 50% inhibited by alpha-tocopherol. No effect of alpha-tocopherol was observed when proliferation of smooth muscle cells was stimulated by bombesin and lysophosphatidic acid. The possibility of an involvement of protein kinase C in the cell response to alpha-tocopherol was suggested by experiments with the isolated enzyme and supported by the 2- to 3-fold stimulation of phorbol ester binding induced by alpha-tocopherol in sensitive cells. Moreover, alpha-tocopherol also caused inhibition of protein kinase C translocation induced by phorbol esters and inhibition of the phosphorylation of its 80-kDa protein substrate in smooth muscle cells. A model is discussed by which alpha-tocopherol inhibits cell proliferation by interacting with the cytosolic protein kinase C, thus preventing its membrane translocation and activation.