ArticleTranslational oncology2017
Acriflavine Inhibits Acquired Drug Resistance by Blocking the Epithelial-to-Mesenchymal Transition and the Unfolded Protein Response.
Article in Translational oncology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.
- New Hope for Pancreatic Ductal Adenocarcinoma Treatment Targeting Endoplasmic Reticulum Stress Response: A Systematic Review.International journal of molecular sciences · 2018Pooled it
- Pathway-specific mechanisms, therapeutic applications, and toxicodynamic profile of acriflavine in cancer: a comprehensive review.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Pathway-specific mechanisms, therapeutic applications, and toxicodynamic profile of acriflavine in cancer: a comprehensive review.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Targeting the SMURF2-HIF1α axis: a new frontier in cancer therapy.Frontiers in oncology · 2024Review
- Human pancreatic cancer patients with Epithelial-to-Mesenchymal Transition and an aggressive phenotype show a disturbed balance in Protein Phosphatase Type 2A expression and functionality.Journal of translational medicine · 2023Article
- Acriflavine, a HIF-1 inhibitor, preserves vision in an experimental autoimmune encephalomyelitis model of optic neuritis.Frontiers in immunology · 2023Article
- Crosstalk between endoplasmic reticulum stress and multidrug-resistant cancers: hope or frustration.Frontiers in pharmacology · 2023Review
- HIF1 inhibitor acriflavine rescues early-onset preeclampsia phenotype in mice lacking placental prolyl hydroxylase domain protein 2.JCI insight · 2022Article
- Acriflavine, an Acridine Derivative for Biomedical Application: Current State of the Art.Journal of medicinal chemistry · 2022Review
- Review
- Hypoxia activates the unfolded protein response signaling network: An adaptive mechanism for endometriosis.Frontiers in endocrinology · 2022Review
- The Activation of the Tumor Suppressor Protein p53 by Acriflavine Leads to Mitochondrial Dysfunction and Improves the Radiosensitivity of Colon Cancer Cells.Journal of immunology research · 2022Article
- Synergism of a novel MCL‑1 downregulator, acriflavine, with navitoclax (ABT‑263) in triple‑negative breast cancer, lung adenocarcinoma and glioblastoma multiforme.International journal of oncology · 2022Article
- Hypoxia-induced therapy resistance: Available hypoxia-targeting strategies and current advances in head and neck cancer.Translational oncology · 2021Review
- Review
- Article
- Stresses in the metastatic cascade: molecular mechanisms and therapeutic opportunities.Genes & development · 2020Review
- Morphometric Assessment of Confocal Laser Endomicroscopy for Pancreatic Ductal Adenocarcinoma, an Ex-Vivo Pilot Study.Diagnostics (Basel, Switzerland) · 2020Article
- Acriflavine targets oncogenic STAT5 signaling in myeloid leukemia cells.Journal of cellular and molecular medicine · 2020Article
- Anti-Cancer Activity of Acriflavine as Metabolic Inhibitor of OXPHOS in Pancreas Cancer Xenografts.OncoTargets and therapy · 2020Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epithelial-to-mesenchymal transition (EMT) is linked to tumor invasion, drug resistance and aggressive disease and this is largely dependent on the cell's microenvironment. Acriflavine (ACF) is an old antibacterial drug recently also suggested as anticancer agent and HIF inhibitor. We wanted to study the effect of acriflavine on EMT in different human cancer models. Pancreatic cancer cells (Panc-1) were exposed to TGF-β1 or cobalt chloride (to mimick severe hypoxia) to induce EMT. For our third model we exposed HepG2 liver cancer cells to sorafenib which resulted in development of acquired drug resistance with strong features of EMT and aggressive behavior. These models were morphologically and functionally (invasion assay) characterized. Markers of EMT were determined using qRT-PCR and Western blotting. Transcriptome analysis was performed following gene expression determination and combining the iRegulon tool and Gene Set Enrichment Analysis (GSEA). We made the following observations: (1) acriflavine inhibited EMT based on changes in cell morphology, invasive capacities and markers of EMT (at protein and gene expression level). (2) Transcriptome analysis revealed potent inhibition of ATF4 target genes and of the unfolded protein response. We showed that acriflavine blocked eIF2a phosphorylation and reduced ATF4 translation thereby inhibiting the PERK/eIF2a/ATF4 UPR pathway. (3) ACF restored drug sensitivity of cells that obtained acquired resistance.
conclusionsWe identified acriflavine as a potent inhibitor of EMT and the UPR, thereby re-sensitizing the cancer cells to antineoplastic drugs.
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.