Novel insights into the antiproliferative effects and synergism of quercetin and menadione in human leukemia Jurkat T cells
Abstract The flavonoid quercetin and menadione (vitamin K3 ) are known as potent apoptogens in human leukemia Jurkat T cells. We explored some underlying mechanisms and the potential relevance of the combination quercetin–menadione for clinical applications. In acute treatments, quercetin manifested...
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Published in | Leukemia research Vol. 38; no. 7; pp. 836 - 849 |
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Main Authors | , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
England
Elsevier Ltd
01.07.2014
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Subjects | |
Online Access | Get full text |
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Summary: | Abstract The flavonoid quercetin and menadione (vitamin K3 ) are known as potent apoptogens in human leukemia Jurkat T cells. We explored some underlying mechanisms and the potential relevance of the combination quercetin–menadione for clinical applications. In acute treatments, quercetin manifested a strong antioxidant character, but induced a transient loss of Δ ψm , likely mediated by opening of the mitochondrial permeability transition pore. After removal of quercetin, persistent mitochondrial hyperpolarization was generated via stimulation of respiratory Complex I. In contrast, menadione-induced Δ ψm dissipation was only partially and transiently reversed after menadione removal. Results indicate that Ca2+ release is a necessary event in quercetin-induced cell death and that the survival response to quercetin is delineated within 1 h from exposure. Depending on dose, the two agents exhibited either antagonistic or synergistic effects in reducing clonogenicity of Jurkat cells. 24-h combinatorial regimens at equimolar concentrations of 10–15 μM, which are compatible with a clinically achievable (and safe) scheme, reduced cell viability at efficient rates. Altogether, these findings support the idea that the combination quercetin–menadione could improve the outcome of conventional leukemia therapies, and warrant the utility of additional studies to investigate the therapeutic effects of this combination in different cellular or animal models for leukemia. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1 |
ISSN: | 0145-2126 1873-5835 |
DOI: | 10.1016/j.leukres.2014.04.010 |