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 journalArticle

    275 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

    Keywords

    • Cancer
    • Chemotherapy
    • Hypoxia
    • Xenograft

    ASJC Scopus subject areas

    • General

    Fingerprint Dive into the research topics of 'Acriflavine inhibits HIF-1 dimerization, tumor growth, and vascularization'. Together they form a unique fingerprint.

  • Cite this