Phytonutrients Differentially Stimulate NAD(P)H:Quinone Oxidoreductase, Inhibit Proliferation, and Trigger Mitotic Catastrophe in Hepa1c1c7 Cells.
Phytonutrients Differentially Stimulate NAD(P)H:Quinone Oxidoreductase, Inhibit Proliferation, and Trigger Mitotic Catastrophe in Hepa1c1c7 Cells.
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DOI：
10.1089/jmf.2015.0079
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发表时间：
2016-01
影响因子：
2.4
通讯作者：
Steven J T Jackson;K. Singletary;L. Murphy;R. Venema;A. Young
中科院分区：
文献类型：
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作者：
Steven J T Jackson;K. Singletary;L. Murphy;R. Venema;A. Young
未标记的植物营养素已迅速成为天然食品化学品，具有多方面的生物作用，可支持有益的健康结果。在目前正在研究的大量植物营养素中，萝卜硫素、姜黄素、槲皮素和白藜芦醇经常被报道可以刺激内源性解毒酶的表达，从而促进中和其他有害的环境因子。然而，这些相同的植物营养素中的一些也与破坏正常细胞增殖有关，因此它们本身可能具有毒性。在这项研究中，我们的特征分别在Hepa 1c 1c 7细胞，刺激NAD（P）H醌氧化还原酶（NQO 1），甲萘醌，其他生物氧化剂，和一些环境致癌物的肝中和的关键酶，上述植物营养素的最低阈值浓度。此外，我们的研究结果表明，相对低浓度的萝卜硫素或姜黄素显着（P <0.05）增加NQO 1蛋白的表达和活性，而不触发G2/M细胞周期停滞或有丝分裂灾难。然而，诱导NQO 1的最小槲皮素浓度比破坏有丝分裂的浓度高100倍。此外，虽然白藜芦醇适度刺激NQO 1，最低限度有效的白藜芦醇浓度伴随诱导细胞凋亡的证据。总之，这些发现表明，只有特定的植物营养素可能有效地上调NQO 1活性，而不会导致肝细胞毒性。
UNLABELLED Phytonutrients have rapidly emerged as natural food chemicals possessing multifaceted biological actions that may support beneficial health outcomes. Among the vast array of phytonutrients currently being studied, sulforaphane, curcumin, quercetin, and resveratrol have been frequently reported to stimulate the expression of endogenous detoxification enzymes and may thereby facilitate the neutralization of otherwise harmful environmental agents. Some of these same phytonutrients, however, have also been implicated in disrupting normal cell proliferation and hence may possess toxic properties in and of themselves. In this study, we characterize the respective minimum threshold concentrations of the aforementioned phytonutrients in Hepa1c1c7 cells that stimulate NAD(P)H quinone oxidoreductase (NQO1), a key enzyme in the hepatic neutralization of menadione, other biological oxidants, and some environmental carcinogens. Moreover, our findings demonstrate that relatively low concentrations of either sulforaphane or curcumin significantly (P < .05) increase NQO1 protein expression and activity without triggering G2/M cell cycle arrest or mitotic catastrophe. The minimal quercetin concentration inducing NQO1, however, was 100-fold higher than that which disrupted mitosis. Also, while resveratrol modestly stimulated NQO1, the minimally effective resveratrol concentration concomitantly induced evidence of cellular apoptosis. Taken together, these findings indicate that only particular phytonutrients are likely efficacious in upregulating NQO1 activity without also leading to hepatic cytotoxicity.