Nrf2 as a Master Redox Switch in Turning on the Cellular Signaling Involved in the Induction of Cytoprotective Genes by Some Chemopreventive Phytochemicals

Abstract

Chemoprevention, a Realistic Strategy to Reduce the Risk of Cancer ! Cancer chemoprevention has attracted much attention as one of the most practical and realistic strategies in reducing the global burden of cancer [1]. The field of cancer chemoprevention research became prominent and focused at the beginning in the late 1960 s when Dr. Lee Wattenberg conceptualized this strategy and suggested a mechanistic framework [2], [3], [4]. A broad spectrum of substances has been reported to retain chemopreventive potential, and it is noticeable that many of them were discovered in the plant kingdom. Numerous phytochemicals derived from fruits, vegetables, grains, spices, and herbs are capable of intervening in multi-stage carcinogenesis via distinct mechanisms [5]. The journey of a population of normal cells towards malignancy apparently involves three distinct stages-initiation, promotion and progression. Tumor initiation, a rapid and irreversible process, begins with the genotoxic damage of cellular DNA upon exposure to endogenous or exogenous carcinogens. The initiation stage of chemically induced tumorigenesis involves the metabolic activation of carcinogens and subsequent

Anthocyanins protect human endothelial cells from mild hyperoxia damage through modulation of Nrf2 pathway

“…Furthermore, the observed protective effect of AS against mild hyperoxia-induced endothelial damage can be ascribed to the activation of the Nrf2/ARE pathway. Our findings are in agreement with those reported by several papers which report that plant phenols can protect endothelial cell against different stressor conditions by pharmacological activation of the Nrf2/ ARE pathway (Speciale et al 2011b;Surh et al 2008). …”

Participation of endoplasmic reticulum stress in the pathogenesis of spontaneous glomerulosclerosis–Role of intra-renal angiotensin system

“…32 This phenomenon represents an important component of adaptive/cytoprotective responses of ER stress to maintain the cellular redox homeostasis. 33 Thus, the observed reduction in PERK abundance and activity may have contributed to the impaired Nrf2 activation in this model. In addition to PERK, phosphorylated Akt can activate Nrf2 and thereby participate in the ER stress-associated prosurvival response.…”

Dose-dependent deleterious and salutary actions of the Nrf2 inducer dh404 in chronic kidney disease

“…Alternatively release and translocation of Nrf2 may occur via phosphorylation of its threonine or serine residues by protein kinase C, mitogen-activated protein kinases, phosphatidylinositol-3-kinase/Akt, casein kinase-2, or the endoplasmic reticulum enzyme PERK [53,54]. BARD analogues promote activation of Nrf2 via covalent modification of the specific thiols in the Keap1 molecules [26].…”