HIF-dependent antitumorigenic effect of antioxidants in vivo

被引：451

作者：

Gao, Ping

Zhang, Huafeng

Dinavahi, Ramani

Li, Feng

Xiang, Yan

Raman, Venu

Bhujwalla, Zaver M.

Felsher, Dean W.

Cheng, Linzhao

Pevsner, Jonathan

Lee, Linda A.

Semenza, Gregg L.

Dang, Chi V. ^{[1
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA

[2] Johns Hopkins Univ, Sch Med, Dept Pediat, Stanford, CA 94305 USA

[3] Johns Hopkins Univ, Sch Med, Dept Neurol, Stanford, CA 94305 USA

[4] Johns Hopkins Univ, Sch Med, Dept Oncol, Stanford, CA 94305 USA

[5] Johns Hopkins Univ, Sch Med, Dept Radiol, Stanford, CA 94305 USA

[6] Johns Hopkins Univ, Sch Med, Inst Cell Engn, Stanford, CA 94305 USA

[7] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Stanford, CA 94305 USA

[8] Stanford Univ, Sch Med, Dept Med & Pathol, Stanford, CA 94305 USA

来源：

CANCER CELL | 2007年 / 12卷 / 03期

关键词：

D O I：

10.1016/j.ccr.2007.08.004

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The antitumorigenic activity of antioxidants has been presumed to arise from their ability to squelch DNA damage and genomic instability mediated by reactive oxygen species (ROS). Here, we report that antioxidants inhibited three tumorigenic models in vivo. Inhibition of a MYC-dependent human B lymphoma model was unassociated with genomic instability but was linked to diminished hypoxia-inducible factor (HIF)-1 levels in a prolyl hydroxylase 2 and von Hippel-Lindau protein-dependent manner. Ectopic expression of an oxygen-independent, stabilized HIF-1 mutant rescued lymphoma xenografts from inhibition by two antioxidants: N-acetylcysteine and vitamin C. These findings challenge the paradigm that antioxidants diminish tumorigenesis primarily through decreasing DNA damage and mutations and provide significant support for a key antitumorigenic effect of diminishing HIF levels.

引用

页码：230 / 238

页数：9

共 39 条

[1] N-acetylcysteine - passe-partout or much ado about nothing? [J].