ArticleLeukemia2008
Downregulation of Mcl-1 potentiates HDACi-mediated apoptosis in leukemic cells.
Article in Leukemia, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 68 citations in OpenAlex.
- Trial
- The anticancer effect of the HDAC inhibitor belinostat is enhanced by inhibitors of Bcl-xMolecular oncology · 2025Article
- Chidamide and venetoclax synergistically regulate the Wnt/β-catenin pathway by MYCN/DKK3 in B-ALL.Annals of hematology · 2025Article
- Chidamide and venetoclax synergistically exert cytotoxicity on multiple myeloma by upregulating BIM expression.Clinical epigenetics · 2022Article
- Article
- Histone Deacetylase Inhibitor SAHA Induces Expression of Fatty Acid-Binding Protein 4 and Inhibits Replication of Human Cytomegalovirus.Virologica Sinica · 2021Article
- Histone Deacetylase Inhibitors as Multitarget-Directed Epi-Drugs in Blocking PI3K Oncogenic Signaling: A Polypharmacology Approach.International journal of molecular sciences · 2020Review
- Resistance to histone deacetylase inhibitors confers hypersensitivity to oncolytic reovirus therapy.Blood advances · 2020Article
- LncRNA FGD5-AS1 promotes tumor growth by regulating MCL1 via sponging miR-153-3p in oral cancer.Aging · 2020Article
- Novel HDAC inhibitor MAKV-8 and imatinib synergistically kill chronic myeloid leukemia cells via inhibition of BCR-ABL/MYC-signaling: effect on imatinib resistance and stem cells.Clinical epigenetics · 2020Article
- Mcl-1 Phosphorylation without Degradation Mediates Sensitivity to HDAC Inhibitors by Liberating BH3-Only Proteins.Cancer research · 2018Article
- Characterization of TET and IDH gene expression in chronic lymphocytic leukemia: comparison with normal B cells and prognostic significance.Clinical epigenetics · 2016Article
- Upregulation of the MCL-1S protein variant following dihydroartemisinin treatment induces apoptosis in cholangiocarcinoma cells.Oncology letters · 2015Article
- Effective elimination of chronic lymphocytic leukemia cells in the stromal microenvironment by a novel drug combination strategy using redox-mediated mechanisms.Molecular medicine reports · 2015Article
- Maritoclax and dinaciclib inhibit MCL-1 activity and induce apoptosis in both a MCL-1-dependent and -independent manner.Oncotarget · 2015Article
- SAHA and S116836, a novel tyrosine kinase inhibitor, synergistically induce apoptosis in imatinib-resistant chronic myelogenous leukemia cells.Cancer biology & therapy · 2014Article
- Synergistic interaction between the HDAC inhibitor, MPT0E028, and sorafenib in liver cancer cells in vitro and in vivo.Clinical cancer research : an official journal of the American Association for Cancer Research · 2014Article
- RNA-dependent dynamic histone acetylation regulates MCL1 alternative splicing.Nucleic acids research · 2014Article
- Apoptosis inducers in chronic lymphocytic leukemia.Oncotarget · 2014Review
- Noxa and cancer therapy: Tuning up the mitochondrial death machinery in response to chemotherapy.Molecular & cellular oncology · 2014Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Mcl-1 is an antiapoptotic Bcl-2 family member, whose degradation is supposedly required for the induction of apoptosis. However, histone deacetylase inhibitors (HDACi) induce apoptosis primarily through the Bak/Mcl-1/Noxa and Bim pathways without decreasing Mcl-1. To investigate this discrepancy, we examined the role of Mcl-1 on HDACi-mediated apoptosis. Inhibition of either class I or class II HDAC by selective HDACi caused an upregulation of Mcl-1 mRNA and protein. Downregulation of Mcl-1 by three structurally unrelated cyclin-dependent kinase inhibitors potentiated HDACi-mediated apoptosis in primary chronic lymphocytic leukemic (CLL) cells and K562 cells. Sensitivity to HDACi-induced apoptosis was increased approximately 10-fold by the cyclin-dependent kinase inhibitors. Nanomolar concentrations of HDACi, approximately 300-fold lower than that required to induce apoptosis alone, sensitized cells to TRAIL, emphasizing that the mechanism(s) whereby HDACi induce apoptosis is clearly distinct from those by which they sensitize to TRAIL. Furthermore, knockdown of Mcl-1-potentiated HDACi-mediated apoptosis in K562 cells. Thus, HDACi-mediated Mcl-1 upregulation plays an important antiapoptotic regulatory role in limiting the efficacy of HDACi-induced apoptosis, which can be overcome by combination with an agent that downregulates Mcl-1. Thus, a clinical trial in some cancers is warranted using a combination of an HDACi with agents that downregulate Mcl-1.
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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.