Nrf2/Keap1/ARE regulation by plant secondary metabolites - a new horizon in brain tumor management

Sep 21, 2026

Uploaded by Rowan

Brain cancer is among the most life-threatening cancers worldwide, and oxidative stress disrupts normal brain homeostasis while contributing to carcinogenesis. The Nrf2/Keap1/ARE signaling pathway coordinates redox homeostasis and modulates anti-inflammatory and anticancer outcomes through multiple downstream routes. Nrf2 can act in opposing ways: as a tumor-suppressing cytoprotective factor under basal insult, yet when hyperactivated it supports survival of both normal and malignant cells and protects them from oxidative stress and therapy. Plant secondary metabolites offer chemotherapeutic or chemopreventive potential by modulating Nrf2/ARE and Keap1-dependent downstream activities, highlighting a new direction for brain tumor management.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages31

Reading Time1 h 18 min

AccessFree to download

Introduction

Brain tumors and current therapeutic challenges

Role of oxidative stress and antioxidants

Nrf2/Keap1/ARE signaling pathway

Keap1-mediated regulation under normoxic conditions

Nrf2 activation during oxidative stress

Dewanjee etal. Cell Communication and Signaling (2024) 22:497 [https://doi.org/10.1186/s12964-024-01878-2](https://doi.org/10.1186/s12964-024-01878-2) Cell Communication and Signaling REVIEW Open Access Nrf2/Keap1/ARE regulation by plant secondary metabolites: a new horizon in brain tumor management Saikat Dewanjee 1*, Hiranmoy Bhattacharya 1, Chiranjib Bhattacharyya 1, Pratik Chakraborty 1, Joshua Fleishman2, Athanasios Alexiou3,4,5,6, Marios Papadakis7* and Saurabh Kumar Jha8* Abstract Brain cancer is regarded as one of the most life-threatening forms of cancer worldwide. Oxidative stress acts to derange normal brain homeostasis, thus is involved in carcinogenesis in brain. The Nrf2/Keap1/ARE pathway isan important signaling cascade responsible for the maintenance of redox homeostasis, and regulation of antiinflammatory and anticancer activities by multiple downstream pathways. Interestingly, Nrf2 plays a somewhat, contradictory role in cancers, including brain cancer. Nrf2 has traditionally been regarded as a tumor suppressor since its cytoprotective functions are considered to be the principle cellular defense mechanism against exogenous and endogenous insults, such as xenobiotics and oxidative stress. However, hyperactivation of the Nrf2 pathway supports the survival of normal as well as malignant cells, protecting them against oxidative stress, and therapeutic agents. Plants possess a pool of secondary metabolites with potential chemotherapeutic/chemopreventive actions. Modulation of Nrf2/ARE and downstream activities in a Keap1-dependant manner, with the aid of plant-derived secondary metabolites exhibits promise in the management of brain tumors. Current article highlights the effects of Nrf2/Keap1/ARE cascade on brain tumors, and the potential role of secondary metabolites regarding the management of the same. Keywords Antioxidants, ARE, Brain cancer, Keap1, Nrf2, Oxidative stress, Secondary metabolites *Correspondence: Saikat Dewanjee[saikat.dewanjee@jadavpuruniversity.in](saikat.dewanjee@jadavpuruniversity.in)[ ](saikat.dewanjee@jadavpuruniversity.in)Marios Papadakis [drmariospapadakis@gmail.com](drmariospapadakis@gmail.com)[ ](drmariospapadakis@gmail.com)Saurabh Kumar Jha[jhasaurabh017@gmail.com](jhasaurabh017@gmail.com) 1Advanced Pharmacognosy Research Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, West Bengal, India 2Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John’s University, New York, NY 11439, USA 3University Centre for Research & Development, Chandigarh University, Chandigarh-Ludhiana Highway, Mohali, Punjab, India 4Department of Research & Development, Funogen, Athens 11741, Greece 5Department of Research & Development, AFNP Med, Wien 1030, Austria 6Department of Science and Engineering, Novel Global Community Educational Foundation, Hebersham, NSW 2770, Australia 7Department of Surgery II, University Hospital Witten-Herdecke, University of Witten-Herdecke, Heusnerstrasse 40, 42283 Wuppertal, Germany 8Department of Zoology, Kalindi College, University of Delhi, Delhi 110008, India © The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence,

FAQs

Why is oxidative stress important in brain cancer?

Oxidative stress deranges brain homeostasis and is involved in brain carcinogenesis, contributing to tumor onset and progression.

What is the Nrf2/Keap1/ARE pathway responsible for?

It is a key signaling cascade that maintains redox homeostasis and regulates anti-inflammatory and anticancer activities via downstream pathways.

How can Nrf2 have both tumor-suppressing and tumor-supporting roles?

Nrf2 is traditionally viewed as a tumor suppressor due to cytoprotective functions against insults, but hyperactivation can support survival of normal and malignant cells and protect them from oxidative stress and therapeutic agents.

Sep 21, 2026

Uploaded by Rowan