RETRACTED: Acriflavine inhibits HIF-1 dimerization, tumor growth, and vascularization (Retracted Article)

被引：410

作者：

Lee, KangAe ^{[1
,2
]}

Zhang, Huafeng ^{[1
,3
]}

Qian, David Z. ^{[1
,3
]}

Rey, Sergio ^{[1
,2
]}

Liu, Jun O. ^{[3
,4
]}

Semenza, Gregg L. ^{[1
,2
,3
,5
,6
,7
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Vasc Program, Inst Cell Engn, Baltimore, MD 21205 USA

[2] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA

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

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

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

[6] Johns Hopkins Univ, Sch Med, Dept Radiat Oncol, Baltimore, MD 21205 USA

[7] Johns Hopkins Univ, Sch Med, Dept Biol Chem, Baltimore, MD 21205 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2009年 / 106卷 / 42期

关键词：

cancer; chemotherapy; hypoxia; xenograft; HYPOXIA; ANGIOGENESIS; BINDING;

D O I：

10.1073/pnas.0909353106

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

HIF-1 is a heterodimeric transcription factor that mediates adaptive responses to hypoxia and plays critical roles in cancer progression. Using a cell-based screening assay we have identified acriflavine as a drug that binds directly to HIF-1 alpha and HIF-2 alpha and inhibits HIF-1 dimerization and transcriptional activity. Pretreatment of mice bearing prostate cancer xenografts with acriflavine prevented tumor growth and treatment of mice bearing established tumors resulted in growth arrest. Acriflavine treatment inhibited intratumoral expression of angiogenic cytokines, mobilization of angiogenic cells into peripheral blood, and tumor vascularization. These results provide proof of principle that small molecules can inhibit dimerization of HIF-1 and have potent inhibitory effects on tumor growth and vascularization.

引用

页码：17910 / 17915

页数：6

共 16 条

[1] Structural basis of ARNT PAS-B dimerization: Use of a common beta-sheet interface for hetero- and homodimerization [J].