ArticleCellular oncology (Dordrecht, Netherlands)2018
Induction of apoptosis via proteasome inhibition in leukemia/lymphoma cells by two potent piperidones.
Article in Cellular oncology (Dordrecht, Netherlands), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 24 citations in OpenAlex.
- Synthesis of Novel Pyrazole-Oxindole Conjugates with Cytotoxicity in Human Cancer Cells via Apoptosis.Chemistry & biodiversity · 2023Article
- Two novel piperidones induce apoptosis and antiproliferative effects on human prostate and lymphoma cancer cell lines.Investigational new drugs · 2022Article
- Ionic liquid-mediated delivery of a BCL-2 inhibitor for topical treatment of skin melanoma.Journal of controlled release : official journal of the Controlled Release Society · 2022Article
- Three novel piperidones exhibit tumor-selective cytotoxicity on leukemia cells via protein degradation and stress-mediated mechanisms.Pharmacological reports : PR · 2022Article
- Cytotoxic Tumour-Selective 1,5-Diaryl-3-Oxo-1,4-Pentadienes Mounted on a Piperidine Ring.Medicines (Basel, Switzerland) · 2021Article
- Design, Synthesis and Tumour-Selective Toxicity of Novel 1-[3-{3,5-Bis(benzylidene)-4-oxo-1-piperidino}-3-oxopropyl]-4-piperidone Oximes and Related Quaternary Ammonium Salts.Molecules (Basel, Switzerland) · 2021Article
- Sensitivity of Acute Myelocytic Leukemia Cells to the Dienone Compound VLX1570 Is Associated with Inhibition of the Ubiquitin-Proteasome System.Biomolecules · 2021Article
- Design, Syntheses, and Bioevaluations of Some NovelMedicines (Basel, Switzerland) · 2021Article
- The Antimalarial Drug Pyronaridine Inhibits Topoisomerase II in Breast Cancer Cells and Hinders Tumor ProgressionClinical cancer drugs · 2021Article
- Synthesis, Molecular Docking and Preliminary Antileukemic Activity of 4-Methoxybenzyl Derivatives Bearing Imidazo[2,1-b][1,3,4]thiadiazole.Chemistry & biodiversity · 2021Article
- Role of Sulfur Metabolism Gene and High-Sulfur Gene Expression in Wool Growth Regulation in the Cashmere Goat.Frontiers in genetics · 2021Article
- Dienone Compounds: Targets and Pharmacological Responses.Journal of medicinal chemistry · 2020Article
- A new pyridazinone exhibits potent cytotoxicity on human cancer cells via apoptosis and poly-ubiquitinated protein accumulation.Cell biology and toxicology · 2019Article
- Article
- Recombinant human lactoferrin induces apoptosis, disruption of F-actin structure and cell cycle arrest with selective cytotoxicity on human triple negative breast cancer cells.Apoptosis : an international journal on programmed cell death · 2019Article
- Thermal inkjet bioprinting triggers the activation of the VEGF pathway in human microvascular endothelial cells in vitro.Biofabrication · 2019Article
- Pyronaridine exerts potent cytotoxicity on human breast and hematological cancer cells through induction of apoptosis.PloS one · 2018Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
Abstract
purposePreviously, compounds containing a piperidone structure have been shown to be highly cytotoxic to cancer cells. Recently, we found that the piperidone compound P2 exhibits a potent anti-neoplastic activity against human breast cancer-derived cells. Here, we aimed to evaluate two piperidone compounds, P1 and P2, for their potential anti-neoplastic activity against human leukemia/lymphoma-derived cells.
methodsCytotoxicity and apoptosis induction were evaluated using MTS, annexin V-FITC/PI and mitochondrial membrane potential polychromatic assays to confirm the mode of action of the piperidone compounds. The effects of compound P1 and P2 treatment on gene expression were assessed using AmpliSeq analysis and, subsequently, confirmed by RT-qPCR and Western blotting.
resultsWe found that the two related piperidone compounds P1 and P2 selectively killed the leukemia/lymphoma cells tested at nanomolar concentrations through induction of the intrinsic apoptotic pathway, as demonstrated by mitochondrial depolarization and caspase-3 activation. AmpliSeq-based transcriptome analyses of the effects of compounds P1 and P2 on HL-60 acute leukemia cells revealed a differential expression of hundreds of genes, 358 of which were found to be affected by both. Additional pathway analyses revealed that a significant number of the common genes were related to the unfolded protein response, implying a possible role of the two compounds in the induction of proteotoxic stress. Subsequent analyses of the transcriptome data revealed that P1 and P2 induced similar gene expression alterations as other well-known proteasome inhibitors. Finally, we found that Noxa, an important mediator of the activity of proteasome inhibitors, was significantly upregulated at both the mRNA and protein levels, indicating a possible role in the cytotoxic mechanism induced by P1 and P2.
conclusionsOur data indicate that the cytotoxic activity of P1 and P2 on leukemia/lymphoma cells is mediated by proteasome inhibition, leading to activation of pro-apoptotic pathways.
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