###### 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 inquire oxidoreductase, heme oxygenase-1, UDP-glucuronosyltransferase, glutathione peroxidase, glutathione-S-transferase, etc. There is accumulating evidence supporting the idea that dietary nutraceuticalids derived from commonly used fruits, vegetables, and spices have the ability to produce cancer chemoprereutive activity by inducing Nrf2-mediated detoxifying enzymes. In this review, we discuss the importance of these nutraceuticalids in cancer chemoprerevention 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 Keep1-Nrf2-ARE signaling system. Keap1; Nrf2; ARE; terpenoid; cancer; chemoprerevention; reactive oxygen species (ROS) +
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Cancer chemopreverutive agents are generally divided into two groups. First, blocking agents, which inhibit the mutagenic initiation of the carcinogenic activity, and second, suppressing agents, which inhibit the further advancement of an existing lesion [6]. Some agents are included in both categories. In addition, blocking agents are again sub-classified into three groups on the basis of their mechanism of action. The first group acts simply by preventing the activation of a carcinogen into its potential carcinogenic form, i.e., prevention of symmetrical dimethylhydrazine-induced neoplasia by disulfiram. The second group increases the activity of the enzyme systems involving the carcinogen detoxification process. The members of the third group act by scavenging and neutralizing the reactive forms of carcinogens, e.g., physiological nucleophile glutathione (GSH) [6]. Popularly known chemopreverity agents, e.g., traditional Chinese medicines, natural compounds, FDA approved drugs, etc., are selective and predisposed to interact with various protein targets with varied signaling pathways in living cells [7]. An increasing amount of evidence is accumulating in which cancer patients have been administered herbs using complementary therapies or dietary components that remarkably interfere with cell signaling [8]. Therefore, chemoprevention is effective with a molecular-level understanding of the factors that initiate and trigger cancer [9]. Over the last several decades, an increasing amount of focus has been put on the molecular origins of cancer. Reactive oxygen species (ROS) are greatly responsible for cancer development, either initiating tumor formation or facilitating cancer cell proliferation [10]. Specifically, increased ROS production accompanies hyperproliferation of tumor cells, and this process is aggravated when oxidative stress hampers the redox balance. Invasive tumor cells achieve this state by enhancing their antioxidant level to help ROS-mediated proliferation, while simultaneously evading ROS thresholds that would facilitate apoptosis, senescence, and ferroptosis [11; 12]. Therefore, cancer cell proliferation can be managed through ROS modulation. The kelch like ECH associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2)- antioxidant response element (ARE) signaling safeguards cells from carcinogenic invasion and restricts cancer development via ROS neutralization [13]. It has been observed in several studies that the Keep1-Nrf2 pathway is mutated in various cancers [14].