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CK2 and PI3K are di...
CK2 and PI3K are direct molecular targets of quercetin in chronic lymphocytic leukaemia.
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- Russo, Maria (författare)
- Institute of Food Sciences, National Research Council, Avellino, Italy;
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- Milito, Alfonsina (författare)
- Institute of Food Sciences, National Research Council, Avellino, Italy;
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- Spagnuolo, Carmela (författare)
- Institute of Food Sciences, National Research Council, Avellino, Italy;
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- Carbone, Virginia (författare)
- Institute of Food Sciences, National Research Council, Avellino, Italy;
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- Rosén, Anders, 1948- (författare)
- Linköpings universitet,Avdelningen för cellbiologi,Medicinska fakulteten
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- Minasi, Paola (författare)
- Institute of Food Sciences, National Research Council, Avellino, Italy;
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- Lauria, Fabio (författare)
- Institute of Food Sciences, National Research Council, Avellino, Italy;
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- Russo, Gian Luigi (författare)
- Institute of Food Sciences, National Research Council, Avellino, Italy;
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(creator_code:org_t)
- 2017-04-19
- 2017
- Engelska.
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Ingår i: Oncotarget. - : Impact Journals LLC. - 1949-2553. ; 8:26, s. 42571-42587
- Relaterad länk:
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https://liu.diva-por... (primary) (Raw object)
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http://www.oncotarge...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
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- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
Nyckelord
- Mcl-1
- PI3K
- chronic lymphocytic leukaemia
- protein kinase CK2
- quercetin
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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