Cancer Chemopreventive Role of Dietary Terpenoids by Modulating Keap1-Nrf2-ARE Signaling System—A Comprehensive Update

Abstract

ROS, RNS, and carcinogenic metabolites generate excessive oxidative stress, which changes the basal cellular status and leads to epigenetic modification, genomic instability, and initiation of cancer. Epigenetic modification may inhibit tumor-suppressor genes and activate oncogenes, enabling cells to have cancer promoting properties. The nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that in humans is encoded by the NFE2L2 gene, and is activated in response to cellular stress. It can regulate redox homoeostasis by expressing several cytoprotective enzymes, including NADPH quinine oxidoreductase, heme oxygenase-1, UDP-glucuronosyltransferase, glutathione peroxidase, glutathione-S-transferase, etc. There is accumulating evidence supporting the idea that dietary nutraceuticals derived from commonly used fruits, vegetables, and spices have the ability to produce cancer chemopreventive activity by inducing Nrf2-mediated detoxifying enzymes. In this review, we discuss the importance of these nutraceuticals in cancer chemoprevention and summarize the role of dietary terpenoids in this respect. This approach was taken to accumulate the mechanistic function of these terpenoids to develop a comprehensive understanding of their direct and indirect roles in modulating the Keap1-Nrf2-ARE signaling system.

Supplementation of syringic acid-rich Phrynium pubinerve leaves imparts protection against allergic inflammatory responses by downregulating iNOS, COX-2, and NF-κB expressions

“…The ROS/RNS scavenging property of EPP might be associated with antioxidative signaling pathways, like kelch-like ECH-associated protein 1(Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE), Nrf2-h eme oxygenase - 1 ( HO-1), etc. which dictate the balancing mechanism between free radicals and antioxidants within the body system [ 71 ]. The antioxidative property of EPP might also be correlated with stabilizing the functions of mast cells and downregulating the gene expression of IL-4 [ 72 , 73 ].…”

Understanding the Antilymphoma Activity of Annona macroprophyllata Donn and Its Acyclic Terpenoids: In Vivo, In Vitro, and In Silico Studies

“…Researchers have suggested that terpenoids may have potential as chemopreventive and therapeutic agents in various types of cancer including liver, mammary, skin, colon, lung, prostate and pancreatic carcinomas [ 14 , 15 , 35 , 38 , 39 ]. The chemopreventive and therapeutic activity of these molecules is achieved by their acting on several signaling pathways that play an important role during the initiation phase of carcinogenesis, by preventing the interaction of carcinogens with DNA, and also in the promotion phase, by generating cell cycle arrest, preventing damage to DNA and inducing apoptosis [ 13 , 14 , 37 , 39 , 42 , 43 ]. Our findings of antilymphoma activity of terpenes isolated from PEAm are consistent with previously published reports.…”

Mushrooms as future generation healthy foods

“…Anti-tumor activity has been demonstrated from several mushroom components including the macromolecular polysaccharides and the highly oxygenated terpenoids, carotenoids, and steroids. The latter are secondary metabolites from mushroom metabolism, which can regulate cell death through multiple pathways including apoptosis, causing tumor cells to self-destruct, a key part of the immune response ( 152 ).…”