ArticleBritish journal of cancer2022
Valproic acid disables the Nrf2 anti-oxidant response in acute myeloid leukaemia cells enhancing reactive oxygen species-mediated killing.
Article in British journal of cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10 citing papers in PubMed, 12 citations in OpenAlex.
- One size does not fit all: An in vitro evaluation of the effects of bezafibrate and medroxyprogesterone acetate on human SH-SY5Y and U-87 MG cancer cells.FEBS open bio · 2026Article
- Valproic Acid Induces Post-Translational Redox Modifications in Mouse Embryos That Are Prevented via Prior Nrf2 Activation.Journal of developmental biology · 2026Article
- A Cisplatin-Based Prodrug Inhibits Nucleotide Excision Repair Independently of Chromatin Accessibility to Overcome Resistance.Biomolecules · 2026Article
- From biosynthesis to function: the roles of ether lipids in cancer development and treatment.Lipids in health and disease · 2025Review
- Sulforaphane protects developing neural networks from VPA-induced synaptic alterations.Molecular psychiatry · 2025Article
- Vorinostat Treatment of Gastric Cancer Cells Leads to ROS-Induced Cell Inhibition and a Complex Pattern of Molecular Alterations in Nrf2-Dependent Genes.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Inhibition of NRF2 enhances the acute myeloid leukemia cell death induced by venetoclax via the ferroptosis pathway.Cell death discovery · 2024Article
- Iron overload induces dysplastic erythropoiesis and features of myelodysplasia in Nrf2-deficient mice.Leukemia · 2024Article
- Immune checkpoints represent a promising breakthrough in targeted therapy and prognosis of myelodysplastic syndrome.Heliyon · 2023Review
- Control of Redox Homeostasis by Short-Chain Fatty Acids: Implications for the Prevention and Treatment of Breast Cancer.Pathogens (Basel, Switzerland) · 2023Review
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Authors and funding
11 authors at 4 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundWe previously demonstrated the in vitro killing of AML cells by the combination of the lipid-lowering agent bezafibrate (BEZ) and the contraceptive hormone medroxyprogesterone acetate (MPA). A phase II trial demonstrated in vivo safety and efficacy of BEZ and MPA (BaP) in elderly, relapsed/refractory AML and high-risk myelodysplastic syndrome (MDS) patients. However, we observed dose-limiting toxicities in a second trial that attempted to improve outcomes via escalation of BaP doses. Thus we sought to identify a third repurposed drug that potentiates activity of low dose BaP (BaP 0.1 mM). METHODS AND
resultsWe demonstrate that addition of a commonly used anti-epileptic, valproic acid (VAL) to low dose BaP (BaP 0.1 mM)(VBaP) enhanced killing of AML cell lines/primary AML cells to levels similar to high dose BaP (BaP 0.5 mM). Similarly, addition of VAL to BaP 0.1 mM enhanced reactive oxygen species (ROS), lipid peroxidation and inhibition of de novo fatty acid synthesis. Overexpression of Nrf2 in K562 and KG1a completely inhibited ROS production and rescued cells from VAL/BaP 0.1 mM/VBaP killing.
conclusionsGiven the good safety data of low-dose BaP in elderly/relapsed/refractory AML patients, and that VAL alone is well-tolerated, we propose VBaP as a novel therapeutic combination for AML.
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