Novel insights into the antiproliferative effects and synergism of quercetin and menadione in human leukemia Jurkat T cells

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• 作者：Irina Baran ; ^{baran@ifin.nipne.ro" class="auth_mail} ; ^{virbaran@yahoo.com" class="auth_mail} ; Diana Ionescu ; Alexandru Filippi ; Maria Magdalena Mocanu ; Adrian Iftime ; Ramona Babes ; Ioana Teodora Tofolean ; Ruxandra Irimia ; Alexandru Goicea ; Valentin Popescu ; Alexandru Dimancea ; Andrei Neagu ; Constanta Ganea
• 关键词：Quercetin ; Menadione ; Rotenone ; Reactive oxygen species ; Mitochondrial depolarization/hyperpolarization ; Leukemia
• 刊名：Leukemia Research
• 出版年：July 2014
• 年：2014
• 卷：38
• 期：7
• 页码：836-849
• 全文大小：4179 K

文摘

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 螖m>蠄m>_m, 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 螖m>蠄m>_m 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 渭M, 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.