Oxidative Stress and Cancer: The Role of Nrf2

Abstract

Oxidative stress due to imbalance between ROS production and detoxification plays a pivotal role in determining cell fate. In response to the excessive ROS, apoptotic signaling pathway is activated to promote normal cell death. However, through deregulation of biomolecules, high amount of ROS promotes carcinogenesis in cells with defective signaling factors. In this line, NRF2 appears to be as a master regulator, which protects cells from oxidative and electrophilic stress. Nrf2 is an intracellular transcription factor that regulates the expression of a number of genes to encode anti-oxidative enzymes, detoxifying factors, anti-apoptotic proteins and drug transporters. Under normal condition, Nrf2 is commonly degraded in cytoplasm by interaction with Keap1 inhibitor as an adaptor for ubiquitination factors. However, high amount of ROS activates tyrosine kinases to dissociate Nrf2: Keap1 complex, nuclear import of Nrf2 and coordinated activation of cytoprotective gene expression. Nevertheless, deregulation of Nrf2 and/or Keap1 due to mutation and activated upstream oncogenes is associated with nuclear accumulation and constitutive activation of Nrf2 to protect cells from apoptosis and induce proliferation, metastasis and chemoresistance. Owning to the interplay of ROS and Nrf2 signaling pathways with carcinogenesis, Nrf2 modulation seems to be important in the personalization of cancer therapy.

Intermittent exposure to whole cigarette smoke alters the differentiation of primary small airway epithelial cells in the air-liquid interface culture

“…Among the top deregulated canonical pathways were Nuclear factor erythroid 2-related factor 2 (NRF2)-mediated oxidative stress, xenobiotic metabolism and aryl hydrocarbon receptor (AHR) signaling [62][63][64][65] . It is known that CS induces reactive oxygen species, which activates the NRF2 pathway 63,66 . Moreover, CS comprises a number of toxic chemicals including polycyclic aromatic hydrocarbons (PAH) 67 .…”

Alantolactone suppresses inflammation, apoptosis and oxidative stress in cigarette smoke-induced human bronchial epithelial cells through activation of Nrf2/HO-1 and inhibition of the NF-κB pathways

“…Nuclear factor erythroid-2-related factor-2 (Nrf2) is a master transcription factor and belongs to the cap 'n' collar subfamily [15]. According to statistics, Nrf2 could mediate genes that encodedrug transporters, antioxidative enzymes, anti-apoptotic proteins and detoxifying factors [16,17]. Moreover, Nrf2 plays a protective role against oxidative stress through regulating antioxidative genes, such as NQO1 and heme oxygenase-1 (HO-1) [18].…”

Structural characterization of peptides fromLocusta migratoria manilensis(Meyen, 1835) and anti-aging effect inCaenorhabditis elegans

“…2 Oxidative stress refers to the imbalance due to excess ROS or oxidants over the capability of the cell to mount an effective antioxidant response. 3 Although the exact biological and cellular mechanisms of the aging process are not well understood, a large body of evidence indicates that oxidative stress plays a key role in aging and aging-related diseases. Production of free radicals is an unavoidable process in the course of cellular metabolism.…”