ArticleOncogene2003
Inhibition of PI-3 kinase sensitizes human leukemic cells to histone deacetylase inhibitor-mediated apoptosis through p44/42 MAP kinase inactivation and abrogation of p21(CIP1/WAF1) induction rather than AKT inhibition.
Article in Oncogene, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 96 citations in OpenAlex.
- A phase I study of vorinostat in combination with idarubicin in relapsed or refractory leukaemia.British journal of haematology · 2010Trial
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- Identification of a novel pyridine derivative with inhibitory activity against ovarian cancer progressionFrontiers in pharmacology · 2022Article
- Molecular Determinants of Cancer Therapy Resistance to HDAC Inhibitor-Induced Autophagy.Cancers · 2019Review
- Antileukemic activity and mechanism of action of the novel PI3K and histone deacetylase dual inhibitor CUDC-907 in acute myeloid leukemia.Haematologica · 2019Article
- p53 at the Crossroads between Different Types of HDAC Inhibitor-Mediated Cancer Cell Death.International journal of molecular sciences · 2019Review
- Epigenetic Targeting of Autophagy via HDAC Inhibition in Tumor Cells: Role of p53.International journal of molecular sciences · 2018Review
- Metabolomic Profiling Reveals Cellular Reprogramming of B-Cell Lymphoma by a Lysine Deacetylase Inhibitor through the Choline Pathway.EBioMedicine · 2018Article
- Histone Deacetylase Inhibitor-Induced Autophagy in Tumor Cells: Implications for p53.International journal of molecular sciences · 2017Review
- Butyrate regulates the expression of inflammatory and chemotactic cytokines in human acute leukemic cells during apoptosis.Cytokine · 2016Article
- Protective effects of butyrate-based compounds on a mouse model for spinal muscular atrophy.Experimental neurology · 2016Article
- Epigenetics in Brain Tumors: HDACs Take Center Stage.Current neuropharmacology · 2016Review
- Class I HDACs Affect DNA Replication, Repair, and Chromatin Structure: Implications for Cancer Therapy.Antioxidants & redox signaling · 2015Review
- Rational Combinations of Targeted Agents in AML.Journal of clinical medicine · 2015Review
- PI3K/mTOR inhibition markedly potentiates HDAC inhibitor activity in NHL cells through BIM- and MCL-1-dependent mechanisms in vitro and in vivo.Clinical cancer research : an official journal of the American Association for Cancer Research · 2014Article
- Article
- Rational combination of dual PI3K/mTOR blockade and Bcl-2/-xL inhibition in AML.Physiological genomics · 2014Review
- Enhanced FGFR signalling predisposes pancreatic cancer to the effect of a potent FGFR inhibitor in preclinical models.British journal of cancer · 2014Article
- The phosphatidylinositol 3-kinases (PI3K) inhibitor GS-1101 synergistically potentiates histone deacetylase inhibitor-induced proliferation inhibition and apoptosis through the inactivation of PI3K and extracellular signal-regulated kinase pathways.British journal of haematology · 2013Article
- A phase I trial of vorinostat and alvocidib in patients with relapsed, refractory, or poor prognosis acute leukemia, or refractory anemia with excess blasts-2.Clinical cancer research : an official journal of the American Association for Cancer Research · 2013Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Effects of the PI-3 kinase inhibitor LY294002 (LY) have been examined in relation to responses of human leukemia cells to histone deacetylase inhibitors (HDIs). Coexposure of U937 cells for 24 h to marginally toxic concentrations of LY294002 (e.g., 30 microM) and sodium butyrate (SB; 1 mM) resulted in a marked increase in mitochondrial damage (e.g., cytochrome c and Smac/DIABLO release, loss of DeltaPsi(m)), caspase activation, and apoptosis. Similar results were observed in Jurkat, HL-60, and K562 leukemic cells and with other HDIs (e.g., SAHA, MS-275). Exposure of cells to SB/LY was associated with Bcl-2 and Bid cleavage, XIAP and Mcl-1 downregulation, and diminished CD11b expression. While LY blocked SB-mediated Akt activation, enforced expression of a constitutively active (myristolated) Akt failed to attenuate SB/LY-mediated lethality. Unexpectedly, treatment of cells with SB+/-LY resulted in a marked reduction in phosphorylation (activation) of p44/42 mitogen-activated protein (MAP) kinase. Moreover, enforced expression of a constitutively active MEK1 construct partially but significantly attenuated SB/LY-induced apoptosis. Lastly, cotreatment with LY blocked SB-mediated induction of p21(CIP1/WAF1); moreover, enforced expression of p21(CIP1/WAF1) significantly reduced SB/LY-mediated apoptosis. Together, these findings indicate that LY promotes SB-mediated apoptosis through an AKT-independent process that involves MEK/MAP kinase inactivation and interference with p21(CIP1/WAF1) induction.
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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.