Journal of Nutritional Science and Vitaminology
Online ISSN : 1881-7742
Print ISSN : 0301-4800
ISSN-L : 0301-4800
Regular Paper
Antiproliferative and Proapoptotic Effects of Tocopherol and Tocol on Activated Hepatic Stellate Cells
Noriko YAMAGUCHIYoshihiro MEZAKIMitsutaka MIURAKatsuyuki IMAIMayako MORIITatsuzo HEBIGUCHIKiwamu YOSHIKAWA
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2011 Volume 57 Issue 5 Pages 317-325

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Abstract

Activated hepatic stellate cells (HSCs) play crucial roles in liver fibrosis. In the course of liver injury, HSCs, which reside in perisinusoidal spaces and lose lipid droplets, morphologically change into a myofibroblastic phenotype and acquire an increased proliferation activity in what is known as the activated state. We have investigated therapeutic strategies for liver fibrosis by promoting spontaneous reversion or inducing apoptosis in activated HSCs. Vitamin E consists of four tocopherols and four tocotrienols, all of which are well-known antioxidants. In this study, the antiproliferative and proapoptotic effects of a tocol, which lacks methyl groups attached to the chromanol ring, and four tocopherols were investigated using activated HSCs. δ-Tocopherol and tocol exhibited relatively high proliferation inhibitory and proapoptotic abilities. However, they did not show proliferation inhibition ability on primary hepatocytes or HepG2 cells. Significant cell detachment was also observed in δ-tocopherol- and tocol-treated HSCs. Decreased protein expressions of α-smooth muscle actin and β1 integrin were observed in a dose-dependent manner. These results indicate that δ-tocopherol and tocol induce anoikis in activated HSCs.

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© 2011 by the Center for Academic Publications Japan
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