Acriflavine Inhibits HIF-1 Dimerization, Tumor Growth, and Vascularization

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2009 Oct 7

PMID 19805192

Citations 261

Authors

KangAe Lee

Huafeng Zhang

David Z Qian

Sergio Rey

Jun O Liu

Gregg L Semenza

Affiliations

Soon will be listed here.

Abstract

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-1alpha and HIF-2alpha 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.

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