Cancer protective role of selected dietary polyphenols via modulating Keap1/Nrf2/ARE and interconnected signaling pathways

Islam, Md Arman and Medha, Maisha Maliha and Un Nahar, Akhlak and Al Fahad, Md Abdullah and Siraj, Md Afjalus and Seidel, Veronique (2023) Cancer protective role of selected dietary polyphenols via modulating Keap1/Nrf2/ARE and interconnected signaling pathways. Nutrition and Cancer, 75 (4). pp. 1065-1102. ISSN 1532-7914 (https://doi.org/10.1080/01635581.2023.2183546)

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Abstract

The Kelch-like ECH associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response elements (ARE) signaling pathway is considered a master regulator of the cellular response against oxidative stress. Numerous studies have investigated the role of Keap1/Nrf2/ARE in the different stages of cancer development. A comprehensive literature search using the Google Scholar, PubMed and Science Direct databases was performed to retrieve information related to the cancer protective role of 21 selected dietary polyphenols via modulation of Keap1/Nrf2/ARE and interconnected signaling pathways/proteins (MAPK/ERK1/2, PI3K/Akt, PKD, JNKs, AMPK, NF-κB). Information on the anti-inflammatory and cytoprotective effects caused by the selected dietary polyphenols following Keap1/Nrf2/ARE modulation was also collected. The majority of the studies analyzed in this review demonstrated the cancer protective role of the selected polyphenols mostly in-vitro. Limited work was performed in-vivo and only one of the selected polyphenols was subjected to a clinical trial. It is hoped that this review will encourage further in-vivo studies to confirm the cancer protective role of methyleugenol, carnosol, and catechin, as well as further clinical trials to unambiguously establish whether the consumption of dietary polyphenols impacts on the incidence and progression of cancers in humans.

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