Regulation of Nrf2/ARE Pathway by Dietary Flavonoids: A Friend or Foe for Cancer Management?
Regulation of Nrf2/ARE Pathway by Dietary Flavonoids: A Friend or Foe for Cancer Management?
复制标题
DOI：
10.3390/antiox9100973
复制
发表时间：
2020-10-11
期刊：
影响因子：
--
通讯作者：
Xu Z
中科院分区：
文献类型：
--
作者：
L Suraweera T;Rupasinghe HPV;Dellaire G;Xu Z
核因子红细胞2相关因子2（Nrf 2）/抗氧化反应元件（ARE）通路是维持人体氧化还原稳态的重要细胞信号转导机制。膳食类黄酮在激活Nrf 2/ARE中与癌症化学预防或癌症促进相关的作用尚未完全确定。在这里，我们总结了黄酮类化合物在癌症化学预防和癌症促进方面的双重作用，对Nrf 2/ARE通路的调节，同时潜在的可能的细胞机制。木犀草素、芹菜素、槲皮素、杨梅素、芸香苷、柚皮素、表儿茶素和染料木黄酮在正常细胞和癌细胞中激活Nrf 2/ARE途径。类黄酮的激素效应已被观察到，由于其抗氧化剂或促氧化剂活性，这取决于浓度。体外和体内研究表明，在正常生理条件下，内源性或外源性刺激激活Nrf 2/ARE通路有助于氧化还原稳态，这可能为癌症化学预防提供了一种机制。然而，一些黄酮类化合物，如木犀草素，芹菜素，杨梅素，槲皮素，柚皮素，表儿茶素，染料木素和大豆苷元，在低浓度（1.5至20 μM）促进癌细胞的生长和增殖体外。特别地，一些类黄酮，包括木犀草素、芹菜素和白杨素，在体外抑制Nrf 2/ARE途径。因此，尽管黄酮类化合物在癌症化学预防中起主要作用，但由于其可能诱导癌细胞生长，因此应系统地研究膳食黄酮类化合物对患者或适当实验动物模型的癌症病理生理学的影响。
The nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway is an important cell signaling mechanism in maintaining redox homeostasis in humans. The role of dietary flavonoids in activating Nrf2/ARE in relation to cancer chemoprevention or cancer promotion is not well established. Here we summarize the dual effects of flavonoids in cancer chemoprevention and cancer promotion with respect to the regulation of the Nrf2/ARE pathway, while underlying the possible cellular mechanisms. Luteolin, apigenin, quercetin, myricetin, rutin, naringenin, epicatechin, and genistein activate the Nrf2/ARE pathway in both normal and cancer cells. The hormetic effect of flavonoids has been observed due to their antioxidant or prooxidant activity, depending on the concentrations. Reported in vitro and in vivo investigations suggest that the activation of the Nrf2/ARE pathway by either endogenous or exogenous stimuli under normal physiological conditions contributes to redox homeostasis, which may provide a mechanism for cancer chemoprevention. However, some flavonoids, such as luteolin, apigenin, myricetin, quercetin, naringenin, epicatechin, genistein, and daidzein, at low concentrations (1.5 to 20 µM) facilitate cancer cell growth and proliferation in vitro. Paradoxically, some flavonoids, including luteolin, apigenin, and chrysin, inhibit the Nrf2/ARE pathway in vitro. Therefore, even though flavonoids play a major role in cancer chemoprevention, due to their possible inducement of cancer cell growth, the effects of dietary flavonoids on cancer pathophysiology in patients or appropriate experimental animal models should be investigated systematically.
登录
查看更多内容
影响因子：
3.4
作者：
Broustas CG;Lieberman HB
通讯作者：
Lieberman HB
影响因子：
1.8
作者：
Apak, Resat;Gorinstein, Shela;Guclu, Kubilay
通讯作者：
Guclu, Kubilay
影响因子：
--
作者：
Basak P;Sadhukhan P;Sarkar P;Sil PC
通讯作者：
Sil PC
影响因子：
64.5
作者：
Chio IIC;Jafarnejad SM;Ponz-Sarvise M;Park Y;Rivera K;Palm W;Wilson J;Sangar V;Hao Y;Öhlund D;Wright K;Filippini D;Lee EJ;Da Silva B;Schoepfer C;Wilkinson JE;Buscaglia JM;DeNicola GM;Tiriac H;Hammell M;Crawford HC;Schmidt EE;Thompson CB;Pappin DJ;Sonenberg N;Tuveson DA
通讯作者：
Tuveson DA
影响因子：
5.6
作者：
Arteaga O;Álvarez A;Revuelta M;Santaolalla F;Urtasun A;Hilario E
通讯作者：
Hilario E