The advancement and development of dietary phytochemicals in cancer chemoprevention research requires the integration of the known, and as-yet-unknown, compounds with the Nrf2-mediated antioxidant, detoxification, and anti-inflammatory systems and their in vitro and in vivo epigenetic mechanisms; human clinical efficacy studies must also be performed.
In this review, we will discuss: the current advances in the study of Nrf2 signaling; Nrf2-deficient tumor mouse models; the epigenetic control of Nrf2 in tumorigenesis and chemoprevention; Nrf2-mediated cancer chemoprevention by naturally occurring dietary phytochemicals; and the mutation or hyper-expression of the Nrf2-Keap1 signaling pathway in advanced tumor cells.
Evidence accumulates that the transcription factor nuclear factor E2-related factor 2 (Nrf2) has an essential role in cancer development and chemoresistance, thus pointing to its potential as an anticancer target and undermining its suitability in chemoprevention.
In addition to several important functions of Nrf2 that lead to cancer chemoprevention, we hypothesize that a mechanical defense of thickened keratin layers may also be a chemopreventive factor because thickened, stratified, squamous epithelium was found on the tongue of Keap1-KD mice.
Collectively, our findings further support the competition model of NRF2 activation and suggest that "ETGE"-containing proteins such as DPP3 contribute to NRF2 activity in cancer.
Reactive oxygen species regulate FSH-induced expression of vascular endothelial growth factor via Nrf2 and HIF1α signaling in human epithelial ovarian cancer.
Since patients have demonstrated individual differences in their response to PDT, Nrf2-mediated transcriptional activation of the ABCG2 gene in cancer may affect patients' responses to PDT as well as chemotherapy.
The aim of this review is to compile and summarize existing knowledge of the oncogenic functions of Nrf2 to provide a solid basis for its potential use as a molecular marker and pharmacological target in cancer.
Given the importance of this pathway to normal thyroid function as well as to cancer; targeted inhibition of NRF2 regulators may impact strategies for therapeutic intervention involving this pathway.
This review provides an overview of (1) the Nrf2-Keap1 signaling pathway, (2) the dual role of Nrf2 in cancer, (3) the molecular basis of Nrf2 activation in cancer cells, and (4) the challenges in the development of Nrf2-based drugs for chemoprevention and chemotherapy.
Recent studies have demonstrated that the expression of NRF2 protein is upregulated in several human malignancies and is associated with worse prognosis in these patients.
A novel CXCR3-B chemokine receptor-induced growth-inhibitory signal in cancer cells is mediated through the regulation of Bach-1 protein and Nrf2 protein nuclear translocation.
The transcription factor Nrf2 is a key regulator of the cellular stress response, and pharmacological Nrf2 activation is a promising strategy for skin protection and cancer prevention.