Ellagic acid and quercetin interact synergistically with resveratrol in the induction of apoptosis and cause transient cell cycle arrest in human leukemia cells
Ellagic acid and quercetin interact synergistically with resveratrol in the induction of apoptosis and cause transient cell cycle arrest in human leukemia cells
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DOI：
10.1016/j.canlet.2004.06.007
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发表时间：
2005-02-10
期刊：
影响因子：
9.7
通讯作者：
Percival, SS
中科院分区：
文献类型：
--
作者：
Mertens-Talcott, SU;Percival, SS
水果和蔬菜中多酚化合物的抗癌作用已得到充分证实。尽管多酚天然以组合形式存在，但关于化合物之间可能的协同或拮抗生化相互作用的信息很少。识别多酚之间的潜在相互作用可以提供有关含多酚食物在癌症预防方面的功效的信息。本研究的目的是研究鞣花酸和槲皮素与白藜芦醇（圆叶葡萄中存在的多酚）的相互作用，假设所选择的多酚在诱导人白血病细胞（MOLT-4）凋亡和减少细胞生长方面协同相互作用。为了检验这一假设，在将鞣花酸、槲皮素和白藜芦醇作为单一化合物和组合一起孵育后，检查了细胞周期动力学、增殖和凋亡（Caspase-3 活性）的变化。结果显示，鞣花酸与白藜芦醇的组合具有超过加性的相互作用，此外，观察到单一化合物和组合诱导的细胞周期动力学的显着改变。进行等辐射线分析以评估鞣花酸与白藜芦醇和槲皮素与白藜芦醇的组合在诱导半胱天冬酶3活性中的明显协同相互作用，证实了鞣花酸和白藜芦醇的组合的组合指数为0.64以及槲皮素和白藜芦醇的组合指数为0.68的协同相互作用。结果表明，含有多酚的食物的抗癌潜力可能并非基于单个化合物的作用，而是可能涉及抗癌作用的协同增强。 (C) 2004 Elsevier Ireland Ltd. 保留所有权利。
Anticarcinogenic effects of polyphenolic compounds in fruits and vegetables are well established. Although polyphenols naturally occur as combinations, little information is available regarding possible synergistic or antagonistic biochemical interactions between compounds. Identifying potential interactions between polyphenols may provide information regarding the efficiency of polyphenol-containing foods in cancer prevention. The objective of this study was to investigate the interactions of ellagic acid and quercetin with resveratrol, polyphenols which occur in muscadine grapes, with the hypothesis that the selected polyphenols would interact synergistically in the induction of apoptosis and reduction of cell growth in human leukemia cells (MOLT-4). To test this hypothesis, alterations in cell cycle kinetics, proliferation, and apoptosis (caspase-3 activity) were examined after incubation with ellagic acid, quercetin, and resveratrol as single compounds and in combination. Results showed a more than additive interaction for the combination of ellagic acid with resveratrol and furthermore, significant alterations in cell cycle kinetics induced by single compounds and combinations were observed. An isobolographic analysis was performed to assess the apparent synergistic interaction for the combinations of ellagic acid with resveratrol and quercetin with resveratrol in the induction of caspase 3 activity, confirming a synergistic interaction with a combination index of 0.64 for the combination of ellagic acid and resveratrol and 0.68 for quercetin and resveratrol. Results indicate that the anticarcinogenic potential of foods containing polyphenols may not be based on the effects of individual compounds, but may involve a synergistic enhancement of the anticancer effects. (C) 2004 Elsevier Ireland Ltd. All rights reserved.