Acriflavine inhibits HIF-1 dimerization, tumor growth, and vascularization

Kang Ae Lee, Huafeng Zhang, David Z. Qian, Sergio Rey, Jun O. Liu, Gregg L. Semenza

Research output: Contribution to journalArticlepeer-review

337 Scopus citations

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-1α and HIF-2α 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.

Original languageEnglish (US)
Pages (from-to)17910-17915
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number42
DOIs
StatePublished - Oct 20 2009
Externally publishedYes

Keywords

  • Cancer
  • Chemotherapy
  • Hypoxia
  • Xenograft

ASJC Scopus subject areas

  • General

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