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.

中文翻译：

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膳食类黄酮对Nrf2 / ARE途径的调节：癌症治疗的朋友还是敌人？

核因子红系2相关因子2（Nrf2）/抗氧化反应元件（ARE）途径是维持人类氧化还原稳态的重要细胞信号传导机制。饮食中的类黄酮在激活Nrf2 / ARE方面与癌症化学预防或癌症促进相关的作用尚未完全确立。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对Nrf2 / ARE途径的调节的双重作用，同时也暗示了可能的细胞机制。木犀草素，芹菜素，槲皮素，杨梅素，芦丁，柚皮素，表儿茶素和金雀异黄素激活正常和癌细胞中的Nrf2 / ARE途径。由于黄酮类化合物的抗氧化剂或原抗氧化剂活性（取决于浓度），已观察到它们的镇痛作用。体外和体内研究的报道表明，在正常生理条件下，内源性或外源性刺激对Nrf2 / ARE途径的激活有助于氧化还原稳态，这可能为癌症的化学预防提供了一种机制。但是，低浓度（1.5至20 µM）的一些类黄酮，如木犀草素，芹菜素，杨梅素，槲皮素，柚皮素，表儿茶素，染料木黄酮和黄豆苷元，可促进癌细胞在体外的生长和增殖。矛盾的是，一些黄酮类化合物，包括木犀草素，芹菜素和chrysin，在体外抑制Nrf2 / ARE途径。因此，即使类黄酮由于可能诱导癌细胞生长而在癌症化学预防中起主要作用，