ArticleBritish journal of cancer2011
Quercetin downregulates Mcl-1 by acting on mRNA stability and protein degradation.
Article in British journal of cancer, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 57 citations in OpenAlex.
- Anti-inflammatory potential of Aronia melanocarpa leaf phenolic extract via NF-κB pathway suppression in LPS-stimulated RAW264.7 macrophages.Molecular biology reports · 2026Article
- Quercetin and hematological cancers: where are we and where are we going?Molecular biology reports · 2025Review
- Synthesis and Biological Evaluation of Quercetagetin Derivatives as the Inhibitors of Mcl-1 and Bcl-2 Against Leukemia.International journal of molecular sciences · 2025Article
- Synergistic Combination of Quercetin and Mafosfamide in Treatment of Bladder Cancer Cells.Molecules (Basel, Switzerland) · 2024Article
- Bioactive Phytoconstituents and Their Therapeutic Potentials in the Treatment of Haematological Cancers: A Review.Life (Basel, Switzerland) · 2023Review
- mTORC1/ERK1/2 Interplay Regulates Protein Synthesis and Survival in Acute Myeloid Leukemia Cell Lines.Biology · 2023Article
- Inhibition of casein kinase 2 sensitizes mantle cell lymphoma to venetoclax through MCL-1 downregulation.Haematologica · 2023Article
- The potential anti-cancer effects of quercetin on blood, prostate and lung cancers: An update.Frontiers in immunology · 2023Review
- Elucidating the Synergistic Effect of Multiple Chinese Herbal Prescriptions in the Treatment of Post-stroke Neurological Damage.Frontiers in pharmacology · 2022Article
- Polyphenolic Flavonoid Compound Quercetin Effects in the Treatment of Acute Myeloid Leukemia and Myelodysplastic Syndromes.Molecules (Basel, Switzerland) · 2021Review
- The genotoxicity potential of luteolin is enhanced by CYP1A1 and CYP1A2 in human lymphoblastoid TK6 cells.Toxicology letters · 2021Article
- Quercetin shortened survival of radio-resistant B-1 cellsOncotarget · 2021Article
- Proteomic Analysis of Quercetin-Treated K562 Cells.International journal of molecular sciences · 2019Article
- Metformin-induced apoptosis facilitates degradation of the cellular caspase 8 (FLICE)-like inhibitory protein through a caspase-dependent pathway in human renal cell carcinoma A498 cells.Oncology letters · 2018Article
- CK2 and PI3K are direct molecular targets of quercetin in chronic lymphocytic leukaemia.Oncotarget · 2017Article
- Established Human Cell Lines as Models to Study Anti-leukemic Effects of Flavonoids.Current genomics · 2017Article
- Early downregulation of Mcl-1 regulates apoptosis triggered by cardiac glycoside UNBS1450.Cell death & disease · 2015Article
- Quercetin Decreases Claudin-2 Expression Mediated by Up-Regulation of microRNA miR-16 in Lung Adenocarcinoma A549 Cells.Nutrients · 2015Article
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundWe recently demonstrated that quercetin, a flavonoid naturally present in food and beverages belonging to the large class of phytochemicals, was able to sensitise leukaemic cells isolated from patients with chronic lymphocytic leukaemia (CLL) when associated with recombinant tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) or anti-CD95. We also showed that quercetin potentiated the effect of fludarabine on resistant B cells from CLL patients. Resistance to therapy in CLL depends on the expression and activity of anti-apoptotic proteins of the Bcl-2 family. Among these, myeloid cell leukaemia-1 (Mcl-1) has been associated with apoptotic resistance in CLL. Therefore, we investigate here whether the sensitising activity of this flavonoid, which leads to increased apoptosis in both cell lines and CLL, could be related to Mcl-1 expression and stability.
resultsB cells isolated from CLL patients showed different levels of Mcl-1 protein expression, resulting, in several cases, in increased sensitivity to fludarabine. Quercetin significantly enhanced the downregulation of Mcl-1 in B cells isolated from selected patients expressing detectable levels of Mcl-1. In U-937 cells, quercetin increased Mcl-1 mRNA instability in the presence of actinomycin D. When cells were treated with MG-132, a proteasome inhibitor, Mcl-1 protein level increased. However, quercetin, in the presence of Z-Vad-FMK, continued to lower Mcl-1 protein expression, indicating its independence from caspase-mediated degradation. In contrast, co-treatment of quercetin and MG-132 did not revert the effect of MG-132 mono-treatment, thus suggesting a possible interference of quercetin in regulating the proteasome-dependent degradation of Mcl-1. Gossypol, a small-molecule inhibitor of Bcl-2 family members, mimics the activity of quercetin by lowering Mcl-1 expression and sensitising U-937 cells to apoptosis induced by recombinant TRAIL and the Fas-ligand.
conclusionThis study demonstrates that in U-937 cells, quercetin downregulates Mcl-1 acting directly or indirectly on its mRNA stability and protein degradation, suggesting that the same mechanism may bypass resistance to apoptosis in leukaemic cells isolated from CLL patients and sensitise B cells to apoptosis induced by drugs and death receptor inducers.
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