ArticleBritish journal of haematology2010
The NF (Nuclear factor)-κB inhibitor parthenolide interacts with histone deacetylase inhibitors to induce MKK7/JNK1-dependent apoptosis in human acute myeloid leukaemia cells.
Article in British journal of haematology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 67 citations in OpenAlex.
- Bortezomib interacts synergistically with belinostat in human acute myeloid leukaemia and acute lymphoblastic leukaemia cells in association with perturbations in NF-κB and Bim.British journal of haematology · 2011Trial
- OxLDL drives pro-inflammatory and foam cell-prone macrophage reprogramming via NF-κB/HIF-1β-dependent metabolic rewiring.Frontiers in cardiovascular medicine · 2026Article
- Prediction of the Binding to the Nuclear Factor NF-Kappa-B by Constituents fromCurrent issues in molecular biology · 2025Article
- Parthenolide: pioneering new frontiers in hematological malignancies.Frontiers in pharmacology · 2025Review
- Sesquiterpene lactones and cancer: new insight into antitumor and anti-inflammatory effects of parthenolide-derived Dimethylaminomicheliolide and Micheliolide.Frontiers in pharmacology · 2025Review
- Progress in discovery and development of natural inhibitors of histone deacetylases (HDACs) as anti-cancer agents.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
- Inhibitory effect of parthenolide on peripheral nerve degeneration.Anatomical science international · 2023Article
- Natural Bioactive Compounds Targeting Histone Deacetylases in Human Cancers: Recent Updates.Molecules (Basel, Switzerland) · 2022Review
- Parthenolide leads to proteomic differences in thyroid cancer cells and promotes apoptosis.BMC complementary medicine and therapies · 2022Article
- Dual-Targeted Therapy Circumvents Non-Genetic Drug Resistance to Targeted Therapy.Frontiers in oncology · 2022Review
- The Emerging Potential of Parthenolide Nanoformulations in Tumor Therapy.Drug design, development and therapy · 2022Review
- Sesquiterpene Lactones and Cancer: New Insight into Antitumor and Anti-inflammatory Effects of Parthenolide-Derived Dimethylaminomicheliolide and Micheliolide.Computational and mathematical methods in medicine · 2022Review
- Natural Bioactive Compounds Targeting Epigenetic Pathways in Cancer: A Review on Alkaloids, Terpenoids, Quinones, and Isothiocyanates.Nutrients · 2021Review
- Histone Deacetylase Inhibitors in the Treatment of Hepatocellular Carcinoma: Current Evidence and Future Opportunities.Journal of personalized medicine · 2021Review
- Parthenolide as Cooperating Agent for Anti-Cancer Treatment of Various Malignancies.Pharmaceuticals (Basel, Switzerland) · 2020Review
- Collateral Sensitivity of Parthenolide via NF-κB and HIF-α Inhibition and Epigenetic Changes in Drug-Resistant Cancer Cell Lines.Frontiers in pharmacology · 2019Article
- Enhanced cytotoxicity of human hepatocellular carcinoma cells following pretreatment with sorafenib combined with trichostatin A.Oncology letters · 2019Article
- Chronic low dose ethanol induces an aggressive metastatic phenotype in TRAMP mice, which is counteracted by parthenolide.Clinical & experimental metastasis · 2018Article
- MMB triazole analogs are potent NF-κB inhibitors and anti-cancer agents against both hematological and solid tumor cells.European journal of medicinal chemistry · 2018Article
- ARNT/HIF-1β links high-risk 1q21 gain and microenvironmental hypoxia to drug resistance and poor prognosis in multiple myeloma.Cancer medicine · 2018Article
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Interactions between the nuclear factor (NF)-κB inhibitor parthenolide and the pan-histone deacetylase inhibitors (HDACIs) vorinostat and LBH589 were investigated in human acute myeloid leukaemia (AML) cells, including primary AML blasts. Co-administration of parthenolide blocked HDACI-mediated phosphorylation/activation of IKK and RelA/p65 in association with increased JNK1 activation in various AML cell types. These events were accompanied by an increase in apoptosis in multiple AML cell lines (e.g. U937, HL-60, NB4, MV-4-11, and MOLM-13). Significantly, parthenolide also increased HDACI-mediated cell death in haematopoietic cells transduced with the MLL-MLLT1 fusion gene, which exhibit certain leukaemia-initiating cell characteristics, as well as primary AML blasts. Exposure to parthenolide/HDACI regimens clearly inhibited the growth of AML-colony-forming units but was relatively sparing toward normal haematopoietic progenitors. Notably, blockade of c-Jun N-terminal kinase (JNK) signalling by either pharmacological inhibitors or genetic means (e.g. dominant-negative JNK1 or JNK1 shRNA) diminished parthenolide/HDACI-mediated lethality. Moreover, dominant-negative MKK7, but not dominant-negative MKK4/SEK1, blocked JNK1 activation and apoptosis induced by parthenolide/HDACI regimens. Together, these findings indicate that parthenolide potentiates HDACI lethality in human AML cells through a process involving NF-κB inhibition and subsequent MKK7-dependent activation of the SAPK/JNK pathway. They also raise the possibility that this strategy may target leukaemic progenitor cells.
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Registered trials
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