title: Antiproliferative and proapoptotic effects of tocopherol and tocol on activated hepatic stellate cells.
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.
authors.affiliation: Department of Cell Biology and Morphology, Akita University Graduate School of Medicine, Akita, Japan. norika-y@gipc.akita-u.ac.jp
authors.forename: Noriko
authors.initials: N
authors.lastname: Yamaguchi
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Mezaki
authors.forename: Mitsutaka
authors.initials: M
authors.lastname: Miura
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Imai
authors.forename: Mayako
authors.initials: M
authors.lastname: Morii
authors.forename: Tatsuzo
authors.initials: T
authors.lastname: Hebiguchi
authors.forename: Kiwamu
authors.initials: K
authors.lastname: Yoshikawa
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D023102:Anoikis / Q000187:drug effects*; D000975:Antioxidants / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D001692:Biological Transport; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D019587:Dietary Supplements; D056945:Hep G2 Cells; D055166:Hepatic Stellate Cells / Q000187:drug effects* / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D039222:Integrin alpha1beta1 / Q000378:metabolism; D008103:Liver Cirrhosis / Q000178:diet therapy / Q000188:drug therapy; D008297:Male; D008745:Methylation; D051381:Rats; D017208:Rats, Wistar; D024505:Tocopherols / Q000737:chemistry / Q000378:metabolism*
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D000975:Antioxidants; D039222:Integrin alpha1beta1; D024505:Tocopherols; C572520:tocol