α-Tocopheryl succinate induces cytostasis and apoptosis in osteosarcoma cells:: the role of E2F1

被引:19
作者
Alleva, R [1 ]
Benassi, MS
Tomasetti, M
Gellert, N
Ponticelli, F
Borghi, B
Picci, P
Neuzil, T
机构
[1] Rizzoli Orthopaed Inst, Dept Anaesthesiol, I-40100 Bologna, Italy
[2] Rizzoli Orthopaed Inst, Dept Muscoloskeletal Oncol, I-40100 Bologna, Italy
[3] Polytech Univ Marche, Dept Mol Pathol & Innovat Therapies, I-60100 Ancona, Italy
[4] Griffith Univ, Sch Med Sci, Apoptosis Res Grp, Southport, Qld 9726, Australia
[5] Acad Sci Czech Republ, Inst Mol Genet, Lab Cell Signalling & Apoptosis, Prague, Czech Republic
基金
澳大利亚研究理事会;
关键词
osteosarcoma; proliferation; apoptosis; alpha-tocopheryl succinate; E2Fl; p53;
D O I
10.1016/j.bbrc.2005.04.080
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
alpha-Tocophervl succinate (alpha-TOS), a redox-inactive analog of vitamin E, induces cell cycle arrest, differentiation, and triggers apoptosis. We examined the ability of alpha-TOS to induce cytostasis and/or apoptosis in two human osteosarcoma cell lines, which carry wild-type pRb but differ in tae p53 status. In the wt-p53 cells, alpha-TOS induced apoptosis, which was associated with p53 activation and enhanced E2F1 expression. Mutant p53 cells failed to undergo apoptosis when challenged with alpha-TOS. The cell growth arrest after alpha-TOS treatment was associated with a reduced expression of E2F1. Knocking down E2F1 rendered the alpha-TOS-sensitive cells rather resistant to the apoptotic stitlluhts inducing a marked and prolonged cell growth arrest. We conclude that alpha-TOS induces cell Growth arrest or apoptosis involving E2F1. (c) 2005 Elsevier Inc. All rights reserved.
引用
收藏
页码:1515 / 1521
页数:7
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