ArticleOncotarget2017
CK2 and PI3K are direct molecular targets of quercetin in chronic lymphocytic leukaemia.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 76 citations in OpenAlex.
- Genetic and Pathogenic Overlaps Between Autism Spectrum Disorder and Alzheimer's Disease: Evolutionary Features and Opportunities for Drug Repurposing.International journal of molecular sciences · 2025Article
- Quercetin and hematological cancers: where are we and where are we going?Molecular biology reports · 2025Review
- Optimized Synthetic Flavonols Support Senescence Clearance and Lung Fibrosis Resolution.ACS pharmacology & translational science · 2025Article
- Marine-Inspired Ovothiol Analogs Inhibit Membrane-Bound Gamma-Glutamyl-Transpeptidase and Modulate Reactive Oxygen Species and Glutathione Levels in Human Leukemic Cells.Marine drugs · 2025Article
- Insights into the Therapeutic Targets and Molecular Mechanisms ofPharmaceuticals (Basel, Switzerland) · 2025Article
- The role of autophagy in cancer: from molecular mechanism to therapeutic window.Frontiers in immunology · 2025Review
- Synergistic Combination of Quercetin and Mafosfamide in Treatment of Bladder Cancer Cells.Molecules (Basel, Switzerland) · 2024Article
- The Interplay between Heat Shock Proteins and Cancer Pathogenesis: A Novel Strategy for Cancer Therapeutics.Cancers · 2024Review
- An organic extract from ascidianFrontiers in chemistry · 2024Article
- Hydroxyl Group Acetylation of Quercetin Enhances Intracellular Absorption and Persistence to Upregulate Anticancer Activity in HepG2 Cells.International journal of molecular sciences · 2023Article
- Polyherbal and Multimodal Treatments: Kaempferol- and Quercetin-Rich Herbs Alleviate Symptoms of Alzheimer's Disease.Biology · 2023Review
- Article
- Regulation of Cellular Senescence in Type 2 Diabetes Mellitus: From Mechanisms to Clinical Applications.Diabetes & metabolism journal · 2023Review
- Targeting receptor tyrosine kinase signaling: Avenues in the management of cutaneous squamous cell carcinoma.iScience · 2023Review
- Article
- Carotenoid-Enriched Nanoemulsions and γ-Rays Synergistically Induce Cell Death in a Novel Radioresistant Osteosarcoma Cell Line.International journal of molecular sciences · 2022Article
- In silico investigations identified Butyl Xanalterate to competently target CK2α (CSNK2A1) for therapy of chronic lymphocytic leukemia.Scientific reports · 2022Article
- Quercetin and Resveratrol Differentially Decrease Expression of the High-Affinity IgE Receptor (FcεRI) by Human and Mouse Mast Cells.Molecules (Basel, Switzerland) · 2022Article
- Senescence: Pathogenic Driver in Chronic Obstructive Pulmonary Disease.Medicina (Kaunas, Lithuania) · 2022Review
- Targeting Sirt1, AMPK, Nrf2, CK2, and Soluble Guanylate Cyclase with Nutraceuticals: A Practical Strategy for Preserving Bone Mass.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite the encouraging results of the innovative therapeutic treatments, complete remission is uncommon in patients affected by chronic lymphocytic leukaemia, which remains an essentially incurable disease. Recently, clinical trials based on BH3-mimetic drugs showed positive outcomes in subjects with poor prognostic features. However, resistance to treatments occurs in a significant number of patients. We previously reported that the multi-kinase inhibitor quercetin, a natural flavonol, restores sensitivity to ABT-737, a BH3-mimetic compound, in both leukemic cell lines and B-cells isolated from patients. To identify the molecular target of quercetin, we employed a new cell line, HG3, obtained by immortalization of B-cells from a chronic lymphocytic leukaemia patient at the later stage of disease. We confirmed that quercetin in association with ABT-737 synergistically enhances apoptosis in HG3 (combination index < 1 for all fractions affected). We also reported that the cellular uptake of quercetin is extremely rapid, with an intracellular concentration of about 38.5 ng/106 cells, after treatment with 25 μM for 5 min. We demonstrated that the activity of protein kinase CK2, which positively triggers PI3K/Akt pathway by inactivating PTEN phosphatase, is inhibited by quercetin immediately after its addition to HG3 cells (0-2 min). PI3K activity was also inhibited by quercetin within 60 min from the treatment. The combined inhibition of CK2 and PI3K kinase activities by quercetin restored ABT-737 sensitivity and increased lethality in human leukemia cells.
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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.