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.
Highlights
Today, cancer is considered one of the major global health crises
We summarize the information of dietary terpenoids demonstrating a cancer chemopreventive role by direct or indirect modulation of the kelch like ECH associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) signaling system
ZB upregulated the expressions of antioxidant enzymes heme oxygenase-1 (HO-1) and γ glutamate cysteine ligase catalytic subunit (γ-GCLC) via increased nuclear accumulation of Nrf2, and decreased cytosolic Keap1 content by means of the extracellular signal regulated kinase (ERK), Jun N-terminal kinase (JNK), phosphoinositide 3-kinases (PI3K)/AKT, protein kinase C (PKC), and AMP-activated protein kinase (AMPK) signaling pathways [90]
Summary
Cancer is considered one of the major global health crises. It is the second most prominent cause of death in the United States [1]. Signaling safeguards cells from carcinogenic invasion and restricts cancer development via ROS neutralization [13] It has been observed in several studies that the Keap1-Nrf pathway is mutated in various cancers [14]. This evidence, as well as additional information on naturally occurring food constituents and vitamins, has established the idea that diet modification can play vital role to prevent cancer [17]. The chemopreventive mechanisms of the associated up- and downstream signaling molecules of Keap1-Nrf2-ARE signaling are discussed
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