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

IF 8.2 2区 生物学 Q1 CELL BIOLOGY
Saikat Dewanjee, Hiranmoy Bhattacharya, Chiranjib Bhattacharyya, Pratik Chakraborty, Joshua Fleishman, Athanasios Alexiou, Marios Papadakis, Saurabh Kumar Jha
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引用次数: 0

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 is an important signaling cascade responsible for the maintenance of redox homeostasis, and regulation of anti-inflammatory 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.

植物次生代谢物对 Nrf2/Keap1/ARE 的调控:脑肿瘤治疗的新视野。
脑癌被认为是全世界最危及生命的癌症之一。氧化应激会破坏正常的脑平衡,从而参与脑癌的发生。Nrf2/Keap1/ARE 通路是一个重要的信号级联,负责维持氧化还原平衡,并通过多个下游通路调节抗炎和抗癌活性。有趣的是,Nrf2 在包括脑癌在内的癌症中发挥着有些矛盾的作用。Nrf2 传统上被视为肿瘤抑制因子,因为它的细胞保护功能被认为是细胞抵御外源性和内源性损伤(如异种生物毒素和氧化应激)的主要防御机制。然而,Nrf2 通路的过度激活支持正常细胞和恶性细胞的存活,保护它们免受氧化应激和治疗药物的伤害。植物拥有大量具有潜在化疗/化学预防作用的次生代谢产物。借助植物提取的次生代谢物,以依赖 Keap1 的方式调节 Nrf2/ARE 及其下游活动,有望治疗脑肿瘤。本文重点介绍了 Nrf2/Keap1/ARE 级联对脑肿瘤的影响,以及次生代谢物在治疗脑肿瘤方面的潜在作用。
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来源期刊
CiteScore
11.00
自引率
0.00%
发文量
180
期刊介绍: Cell Communication and Signaling (CCS) is a peer-reviewed, open-access scientific journal that focuses on cellular signaling pathways in both normal and pathological conditions. It publishes original research, reviews, and commentaries, welcoming studies that utilize molecular, morphological, biochemical, structural, and cell biology approaches. CCS also encourages interdisciplinary work and innovative models, including in silico, in vitro, and in vivo approaches, to facilitate investigations of cell signaling pathways, networks, and behavior. Starting from January 2019, CCS is proud to announce its affiliation with the International Cell Death Society. The journal now encourages submissions covering all aspects of cell death, including apoptotic and non-apoptotic mechanisms, cell death in model systems, autophagy, clearance of dying cells, and the immunological and pathological consequences of dying cells in the tissue microenvironment.
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