Dual effect of echinomycin on hypoxia‐inducible factor‐1 activity under normoxic and hypoxic conditions
Abstract
Hypoxia-inducible factor-1 (HIF-1) is now recognized as a possible target for cancer treatment. This transcription factor is responsible for the overexpression of several genes favouring cancer cell survival and inducing neo-angiogenesis. Echinomycin has recently been described to inhibit HIF-1 DNA binding and transcriptional activity. In this work, it is shown that echinomycin strongly inhibits the activity of HIF-1 under hypoxic conditions, and also interferes with the activity of other transcription factors. These results demonstrate the lack of specificity of this molecule. Moreover, it is demonstrated that echinomycin induces an increase in HIF-1 activity under normoxic conditions, parallel to an increase in the expression of HIF-1 target genes. This effect is caused by an increase in HIF-1alpha protein level, resulting from an increase in the transcription of the HIF-1A gene in the presence of a low concentration of echinomycin. Transfection experiments with HIF-1alpha promoter constructs revealed the presence of an Sp1 binding element responsive to echinomycin. Furthermore, echinomycin enhanced Sp1 activity, as measured by the use of a specific reporter system. These findings show, for the first time, that echinomycin has a dual effect on HIF-1 activity under normoxic and hypoxic conditions, demonstrating that this molecule cannot be used in cancer treatment.
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Echinomycin also binds DNA motifs recognized by other transcription factors, such as AP-1, NF-κB, or members of the Myc/Max family, whose E-box binding site overlaps substantially with the HIF HRE core.
“Echinomycin also binds DNA motifs recognized by other transcription factors, such as AP-1, NF-κB, or members of the Myc/Max family, whose E-box binding site (5′-CACGTG-3′) overlaps substantially with the HIF HRE core [383,385].”
From HIF inhibition: Current strategies and clinical challenges (2026) · cites this paper as [385]
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- Authors
- Vlaminck, B., Toffoli, S., Ghislain, B., Demazy, C., Raes, M., & Michiels, C.
- Affiliations
- University of Namur (BE)
- Venue
- The FEBS Journal
- Publisher
- Wiley
- Published
- 2007-10-04
- Volume
- 274
- Issue
- 21
- Pages
- 5533-5542
- ISSN
- 1742-464X (ISSN-L)
- 1742-4658
- OpenAlex
- W1859576612
- Cited by
- 61
- References
- 32
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 3 · 2023: 3 · 2022: 6 · 2021: 3 · 2020: 3 · 2019: 3 · 2018: 2 · 2017: 5 · 2016: 3 · 2015: 2 · 2013: 2 · 2012: 7
- FWCI
- 0.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- FEBS Journal (publishedVersion)
- PubMed (publishedVersion)
- DIAL (Catholic University of Leuven) (submittedVersion)
- Repository of the University of Namur (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Kruppel-like factors research
- Keywords
- echinomycin, HIF-1, HIF-1α, hypoxia, normoxic conditions, transcriptional activity, HIF-1 target genes, transcription factor specificity, cancer therapy targets
- MeSH terms
- Antibiotics, Antineoplastic, Echinomycin, Fluorescent Antibody Technique, HeLa Cells, Humans, RNA, Messenger, Transfection, Tumor Cells, Cultured, Cell Hypoxia, Proto-Oncogene Proteins c-myc, Transcription Factor AP-1, Hypoxia-Inducible Factor 1
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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