ArticleJournal of cellular biochemistry2011
Targeting PKC-mediated signal transduction pathways using enzastaurin to promote apoptosis in acute myeloid leukemia-derived cell lines and blast cells.
Article in Journal of cellular biochemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
29 citing papers in PubMed, 45 citations in OpenAlex.
- Serum levels of FAK and some of its effectors in adult AML: correlation with prognostic factors and survival.Molecular and cellular biochemistry · 2021Trial
- Induction of heme oxygenase-1 by Na+-H+ exchanger 1 protein plays a crucial role in imatinib-resistant chronic myeloid leukemia cells.The Journal of biological chemistry · 2015Trial
- Deciphering Multitarget Mechanisms of Cardiac Glycosides in Acute Myeloid Leukemia Using a Network Pharmacology and Molecular Docking.Drug design, development and therapy · 2026Article
- PKC isoforms in hematopoietic lineages and myeloid/lymphoid leukemias: mechanistic insights and therapeutic prospects.Frontiers in oncology · 2026Review
- Galectin-3 Release in the Bone Marrow Microenvironment Promotes Drug Resistance and Relapse in Acute Myeloid Leukemia.Life (Basel, Switzerland) · 2025Review
- The Neuropilin-1/PKC axis promotes neuroendocrine differentiation and drug resistance of prostate cancer.British journal of cancer · 2023Article
- Article
- Deregulated calcium signaling in blood cancer: Underlying mechanisms and therapeutic potential.Frontiers in oncology · 2022Review
- Resistance to Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia-From Molecular Mechanisms to Clinical Relevance.Cancers · 2021Review
- PKCα Inhibition as a Strategy to Sensitize Neuroblastoma Stem Cells to Etoposide by Stimulating Ferroptosis.Antioxidants (Basel, Switzerland) · 2021Article
- Patient-tailored design for selective co-inhibition of leukemic cell subpopulations.Science advances · 2021Article
- Loss of H3K27 methylation identifies poor outcomes in adult-onset acute leukemia.Clinical epigenetics · 2021Article
- The Novel Phospholipid Mimetic KPC34 Is Highly Active Against Acute Myeloid Leukemia with Activated Protein Kinase C.Translational oncology · 2020Article
- Tetraspanin CD82 drives acute myeloid leukemia chemoresistance by modulating protein kinase C alpha and β1 integrin activation.Oncogene · 2020Article
- GSK-J4 induces cell cycle arrest and apoptosis via ER stress and the synergism between GSK-J4 and decitabine in acute myeloid leukemia KG-1a cells.Cancer cell international · 2020Article
- Enzastaurin enhances ATRA-induced differentiation of acute myeloid leukemia cells.American journal of translational research · 2020Article
- Kinase Regulation of HOX Transcription Factors.Cancers · 2019Review
- Combination of enzastaurin and ATRA exerts dose-dependent dual effects on ATRA-resistant acute promyelocytic leukemia cells.American journal of cancer research · 2019Article
- IL-32θ: a recently identified anti-inflammatory variant of IL-32 and its preventive role in various disorders and tumor suppressor activity.American journal of translational research · 2017Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Recent studies in acute myeloid leukemia (AML) suggest activation of pro-proliferative signaling cascades including those mediated by protein kinase C (PKC) represent a poor prognostic factor for patients. The classical PKC isoforms α and β generally support survival signaling and have emerged as important targets for anti-cancer therapy. Enzastaurin is a PKC β inhibitor and is in clinical trials for lymphomas, gliomas, and lung cancer. Presently, it is not known if enzastaurin could be effective against AML. In the current study, we found that high dose enzastaurin was found to promote apoptosis in the AML-derived cell lines and in blast cells from AML patients. The mechanism of cell death, however, likely does not involve PKC β as another PKC β inhibitor was not toxic to AML cell lines and did not promote enzastaurin-induced cell killing. While enzastaurin is fairly specific for PKC β, the agent can inhibit other PKC isoforms at higher concentrations. Enzastaurin was effective at inhibiting PKC α phosphorylation and membrane localization in the AML cell lines and suppressed phosphorylation of BCL2. Furthermore, enzastaurin suppressed activation of ERK (which can be activated by PKC α). Analysis of the serine/threonine phosphorylation profile in HL60 cells after enzastaurin treatment revealed that the drug inhibits the phosphorylation of a distinct set of proteins while promoting phosphorylation of another set of proteins. This suggests the drug may regulate multiple signaling pathways. Taken together, these findings suggest that enzastaurin could be effective in the therapy of AML.
Indexed as
Identifiers
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.