Regulation of Nrf2/ARE Pathway by Dietary Flavonoids: A Friend or Foe for Cancer Management?

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 no...

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Main Authors: Tharindu L. Suraweera (Author), H. P. Vasantha Rupasinghe (Author), Graham Dellaire (Author), Zhaolin Xu (Author)
Format: Book
Published: MDPI AG, 2020-10-01T00:00:00Z.
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001 doaj_8b69a98ee7604eefa03dcc4b6ff5adb6
042 |a dc 
100 1 0 |a Tharindu L. Suraweera  |e author 
700 1 0 |a H. P. Vasantha Rupasinghe  |e author 
700 1 0 |a Graham Dellaire  |e author 
700 1 0 |a Zhaolin Xu  |e author 
245 0 0 |a Regulation of Nrf2/ARE Pathway by Dietary Flavonoids: A Friend or Foe for Cancer Management? 
260 |b MDPI AG,   |c 2020-10-01T00:00:00Z. 
500 |a 10.3390/antiox9100973 
500 |a 2076-3921 
520 |a 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. 
546 |a EN 
690 |a cancer chemoprevention 
690 |a cancer promotion 
690 |a polyphenols 
690 |a oxidative homeostasis 
690 |a Keap1/Nrf2 
690 |a Therapeutics. Pharmacology 
690 |a RM1-950 
655 7 |a article  |2 local 
786 0 |n Antioxidants, Vol 9, Iss 10, p 973 (2020) 
787 0 |n https://www.mdpi.com/2076-3921/9/10/973 
787 0 |n https://doaj.org/toc/2076-3921 
856 4 1 |u https://doaj.org/article/8b69a98ee7604eefa03dcc4b6ff5adb6  |z Connect to this object online.