ArticleCancers2020
Acriflavine, a Potent Inhibitor of HIF-1α, Disturbs Glucose Metabolism and Suppresses ATF4-Protective Pathways in Melanoma under Non-Hypoxic Conditions.
Article in Cancers, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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The trial behind it
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Who cites it
27 citing papers in PubMed, 35 citations in OpenAlex.
- MITF-Driven melanoma plasticity as a core mechanism of therapy resistance: integrating microenvironmental signaling, mechanotransduction, and metabolic reprogramming.Cell cycle (Georgetown, Tex.) · 2026Review
- T cell-derived CCL5 drives macrophage immunometabolic remodeling in chronic prostatitis via the CCR5-ERK-PKM2/HIF-1α axis.Redox biology · 2026Article
- Hypoxia-Inducible Factor-1α Gene (Cancers · 2026Article
- Substrate stiffness regulates HIF-1α signalling via β1-integrin/myosin-2/NF-κB axis.Journal of translational medicine · 2026Article
- HIF-Regulated Pannexin-1 Channel Drives Luminal ATP Accumulation in Kidney Cysts.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Integrated approaches to sensitizing melanoma to radiotherapy.Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] · 2026Review
- Review
- Transcription Factors and Methods for the Pharmacological Correction of Their Activity.International journal of molecular sciences · 2025Review
- Role of the tumor microenvironment in cancer therapy: unveiling new targets to overcome drug resistance.Medical oncology (Northwood, London, England) · 2025Review
- Unraveling the role of hypoxia-inducible factors in cutaneous melanoma: from mechanisms to therapeutic opportunities.Cell communication and signaling : CCS · 2025Review
- Hypoxia-inducible transcription factors: architects of tumorigenesis and targets for anticancer drug discovery.Transcription · 2025Review
- Key Nano-Strategies for Cisplatin Resistance in Advancing Anti-Cancer Therapy.International journal of nanomedicine · 2025Review
- The role of bHLH-PAS transcription factors in endoplasmic reticulum stress.Frontiers in molecular biosciences · 2025Review
- [Immunomodulation in the tumor microenvironment: Therapeutic potential of combined inhibition of tumor hypoxia and PD-1/ PD-L1].Magyar onkologia · 2024Review
- Targeting Hypoxia-Inducible Factor-1 (HIF-1) in Cancer: Emerging Therapeutic Strategies and Pathway Regulation.Pharmaceuticals (Basel, Switzerland) · 2024Review
- A Smart CA IX-Targeting and pH-Responsive Nano-Mixed Micelles for Delivery of FB15 with Superior Anti-Breast Cancer Efficacy.International journal of nanomedicine · 2024Article
- Is acriflavine an efficient co-drug in chemotherapy?RSC advances · 2023Article
- Review
- Tumor-secreted lactate contributes to an immunosuppressive microenvironment and affects CD8 T-cell infiltration in glioblastoma.Frontiers in immunology · 2023Article
- Acriflavine, an Acridine Derivative for Biomedical Application: Current State of the Art.Journal of medicinal chemistry · 2022Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Hypoxia-inducible factor (HIF)-1α is constitutively expressed in melanoma cells under normoxic conditions and its elevated expression correlates with the aggressiveness of melanoma tumors. Here, we used acriflavine, a potent inhibitor of HIF-1α dimerization, as a tool to investigate whether HIF-1α-regulated pathways contribute to the growth of melanoma cells under normoxia. We observed that acriflavine differentially modulated HIF-1α-regulated targets in melanoma under normoxic conditions, although acriflavine treatment resulted in over-expression of vascular endothelial growth factor (VEGF), its action clearly downregulated the expression of pyruvate dehydrogenase kinase 1 (PDK1), a well-known target of HIF-1α. Consequently, downregulation of PDK1 by acrifavine resulted in reduced glucose availability and suppression of the Warburg effect in melanoma cells. In addition, by inhibiting the AKT and RSK2 phosphorylation, acriflavine also avoided protective pathways necessary for survival under conditions of oxidative stress. Interestingly, we show that acriflavine targets activating transcription factor 4 (ATF4) for proteasomal degradation while suppressing the expression of microphthalmia-associated transcription factor (MITF), a master regulator of melanocyte development and a melanoma oncogene. Since acriflavine treatment results in the consistent death of melanoma cells, our results suggest that inhibition of HIF-1α function in melanoma could open new avenues for the treatment of this deadly disease regardless of the hypoxic condition of the tumor.
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Registered trials
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