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

Dietary cancer chemopreventive agents - targeting inflammation and Nrf2 signaling pathway.

Accumulating epidemiological and clinical evidence shows that chronic inflammation plays a critical role in neoplastic transformation and progression. Long-term users of selective cycloxygenase-2 (Cox-2) inhibitors (coxibs) and non-steroidal anti-inflammatory drugs (NSAIDs) have been reported to have a reduced risk of developing colorectal cancer. However, the adverse gastrointestinal and cardi...

Keap1-nrf2 signaling: a target for cancer prevention by sulforaphane.

Sulforaphane is a promising agent under preclinical evaluation in many models of disease prevention. This bioactive phytochemical affects many molecular targets in cellular and animal models; however, amongst the most sensitive is Keap1, a key sensor for the adaptive stress response system regulated through the transcription factor Nrf2. Keap1 is a sulfhydryl-rich protein that represses Nrf2 si...

The Nrf2-Keap1-ARE signaling pathway: The regulation and dual function of Nrf2 in cancer.

The NF-E2-related factor-2 (Nrf2) is a transcription factor that is ubiquitously expressed at low levels in all human organs. As Nrf2 regulates a major cellular defense mechanism, tight regulation is crucial to maintain cellular homeostasis. Activation of this pathway is important in preventing human diseases, such as cancer, neurodegenerative disease, cardiovascular diseases, ischemia, diabete...

Oxidative Stress of Nrf2 by Chemopreventive Agents and Ubiquitination of Nrf2 and for Stabilization Required for Keap1-Dependent Distinct Cysteine Residues in Keap1 Are

Distinct cysteine residues in Keap1 are required for Keap1-dependent ubiquitination of Nrf2 and for stabilization of Nrf2 by chemopreventive agents and oxidative stress.

A common feature of diverse chemopreventive agents is the ability to activate expression of a genetic program that protects cells from reactive chemical species that, if left unchecked, would cause mutagenic DNA damage. The bZIP transcription factor Nrf2 has emerged as a key regulator of this cancer-preventive genetic program. Nrf2 is normally sequestered in the cytoplasm by a protein known as ...