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Published on: September 26, 2019

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

KangAe Lee1, Huafeng Zhang, David Z Qian

  • 1Vascular Program, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Proceedings of the National Academy of Sciences of the United States of America
|October 7, 2009
PubMed

Insights

Acriflavine inhibits hypoxia-inducible factor 1 (HIF-1) dimerization and activity. This drug prevents prostate cancer xenograft growth and reduces tumor vascularization, offering a novel therapeutic strategy.

Area of Science:

  • Molecular Biology
  • Oncology
  • Pharmacology

Background:

  • Hypoxia-inducible factor 1 (HIF-1) is a transcription factor crucial for cellular adaptation to low oxygen conditions.
  • HIF-1 plays a significant role in promoting cancer progression and tumor development.
  • Targeting HIF-1 presents a potential strategy for cancer therapy.

Purpose of the Study:

  • To identify small molecules that inhibit HIF-1 dimerization and transcriptional activity.
  • To evaluate the anti-cancer effects of acriflavine, a novel HIF-1 inhibitor, in preclinical models.

Main Methods:

  • A cell-based screening assay was employed to identify HIF-1 inhibitors.
  • Acriflavine's direct binding to HIF-1alpha and HIF-2alpha was confirmed.
  • Prostate cancer xenograft models in mice were used to assess tumor growth inhibition and vascularization effects.

Main Results:

  • Acriflavine was identified as a direct inhibitor of HIF-1alpha and HIF-2alpha, blocking HIF-1 dimerization and activity.
  • Pretreatment with acriflavine prevented tumor growth in mice with prostate cancer xenografts.
  • Treatment of established tumors with acriflavine led to growth arrest and inhibited tumor vascularization.

Conclusions:

  • Small molecules can effectively inhibit HIF-1 dimerization.
  • Acriflavine demonstrates potent anti-tumor effects by inhibiting HIF-1 and tumor vascularization.
  • Targeting HIF-1 with small molecules like acriflavine offers a promising therapeutic approach for cancer treatment.

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