ArticlePloS one2015
FL3, a Synthetic Flavagline and Ligand of Prohibitins, Protects Cardiomyocytes via STAT3 from Doxorubicin Toxicity.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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.
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Who cites it
22 citing papers in PubMed, 41 citations in OpenAlex.
- PHB2 mitigates intervertebral disc degeneration by modulating mitophagy to inhibit necroptosis in nucleus pulposus cells.iScience · 2026Article
- STAT-Mediated Mitochondrial Regulation in Cardiovascular Diseases: Mechanistic Insights and STAT3-Focused Therapeutic Strategies.Biomolecules · 2026Review
- Prohibitins: emerging host targets of bacteria and viruses at the plasma membrane, mitochondria, and cytoplasm.Microbial cell (Graz, Austria) · 2026Article
- MAMs-Mediated Calcium Homeostasis in the Pathophysiology of Cardiovascular Diseases: A Mini-Review.Drug design, development and therapy · 2026Review
- FL3 mitigates cardiac ischemia-reperfusion injury by promoting mitochondrial fusion to restore calcium homeostasis.Cell death discovery · 2025Article
- MYO1F in neutrophils is required for the response to immune checkpoint blockade therapy.The Journal of experimental medicine · 2025Article
- Loss of prohibitin 2 in Schwann cells dysregulates key transcription factors controlling developmental myelination.bioRxiv : the preprint server for biology · 2024Article
- Targeting Prohibitins to Inhibit Melanoma Growth and Overcome Resistance to Targeted Therapies.Cells · 2023Article
- The function of prohibitins in mitochondria and the clinical potentials.Cancer cell international · 2022Review
- Celastrol and Rhynchophylline in the mitigation of simulated muscle atrophy underSaudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2022Article
- Prohibitin 1 interacts with p53 in the regulation of mitochondrial dynamics and chemoresistance in gynecologic cancers.Journal of ovarian research · 2022Article
- Role of Prohibitins in Aging and Therapeutic Potential Against Age-Related Diseases.Frontiers in genetics · 2021Review
- SFPH proteins as therapeutic targets for a myriad of diseases.Bioorganic & medicinal chemistry letters · 2020Review
- Flavaglines as natural products targeting eIF4A and prohibitins: From traditional Chinese medicine to antiviral activity against coronaviruses.European journal of medicinal chemistry · 2020Review
- Prohibitin ligands: a growing armamentarium to tackle cancers, osteoporosis, inflammatory, cardiac and neurological diseases.Cellular and molecular life sciences : CMLS · 2020Review
- The Synthetic Small Molecule FL3 Combats Intestinal Tumorigenesis via Axin1-Mediated Inhibition of Wnt/β-Catenin Signaling.Cancer research · 2020Article
- Flavagline synthetic derivative induces senescence in glioblastoma cancer cells without being toxic to healthy astrocytes.Scientific reports · 2020Article
- Prohibitin (PHB) expression is associated with aggressiveness in DLBCL and flavagline-mediated inhibition of cytoplasmic PHB functions induces anti-tumor effects.Journal of experimental & clinical cancer research : CR · 2019Article
- Atovaquone enhances doxorubicin's efficacy via inhibiting mitochondrial respiration and STAT3 in aggressive thyroid cancer.Journal of bioenergetics and biomembranes · 2018Article
- Flavagline analog FL3 induces cell cycle arrest in urothelial carcinoma cell of the bladder by inhibiting the Akt/PHB interaction to activate the GADD45α pathway.Journal of experimental & clinical cancer research : CR · 2018Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsThe clinical use of doxorubicin for the treatment of cancer is limited by its cardiotoxicity. Flavaglines are natural products that have both potent anticancer and cardioprotective properties. A synthetic analog of flavaglines, FL3, efficiently protects mice from the cardiotoxicity of doxorubicin. The mechanism underlying this cardioprotective effect has yet to be elucidated. METHODS AND
resultsHere, we show that FL3 binds to the scaffold proteins prohibitins (PHBs) and thus promotes their translocation to mitochondria in the H9c2 cardiomyocytes. FL3 induces heterodimerization of PHB1 with STAT3, thereby ensuring cardioprotection from doxorubicin toxicity. This interaction is associated with phosphorylation of STAT3. A JAK2 inhibitor, WP1066, suppresses both the phosphorylation of STAT3 and the protective effect of FL3 in cardiomyocytes. The involvement of PHBs in the FL3-mediated cardioprotection was confirmed by means of small interfering RNAs (siRNAs) targeting PHB1 and PHB2. The siRNA knockdown of PHBs inhibits both phosphorylation of STAT3 and the cardioprotective effect of FL3.
conclusionActivation of mitochondrial STAT3/PHB1 complex by PHB ligands may be a new strategy against doxorubicin-induced cardiotoxicity and possibly other cardiac problems.
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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.