Dual roles of Nrf2 in cancer

Alexandria Lau, Nicole F. Villeneuve, Zheng Sun, Pak Kin Wong, Donna Zhang

Research output: Contribution to journalArticle

439 Citations (Scopus)

Abstract

In response to oxidative stress, the transcription factor NF-E2-related factor 2 (Nrf2) controls the fate of cells through transcriptional upregulation of antioxidant response element (ARE)-bearing genes, including those encoding endogenous antioxidants, phase II detoxifying enzymes, and transporters. Expression of the Nrf2-dependent proteins is critical for ameliorating or eliminating toxicants/carcinogens to maintain cellular redox homeostasis. As a result, activation of the Nrf2 pathway, by naturally-occurring compounds or synthetic chemicals at sub-toxic doses, confers protection against subsequent toxic/carcinogenic exposure. Thus, the use of dietary compounds or synthetic chemicals to boost the Nrf2-dependent adaptive response to counteract environmental insults has emerged to be a promising strategy for cancer prevention. Interestingly, recent emerging data has revealed the "dark" side of Nrf2. Nrf2 and its downstream genes are overexpressed in many cancer cell lines and human cancer tissues, giving cancer cells an advantage for survival and growth. Furthermore, Nrf2 is upregulated in resistant cancer cells and is thought to be responsible for acquired chemoresistance. Therefore, it may be necessary to inhibit the Nrf2 pathway during chemotherapy. This review is primarily focused on the role of Nrf2 in cancer, with emphasis on the recent findings indicating the cancer promoting function of Nrf2 and its role in acquired chemoresistance.

Original languageEnglish (US)
Pages (from-to)262-270
Number of pages9
JournalPharmacological Research
Volume58
Issue number5-6
DOIs
StatePublished - Nov 2008

Fingerprint

NF-E2-Related Factor 2
Neoplasms
Poisons
Antioxidant Response Elements
Carcinogens
Genes
Oxidation-Reduction
Cell Survival
Oxidative Stress
Homeostasis
Transcription Factors
Up-Regulation
Antioxidants

Keywords

  • ARE
  • Glutamate cysteine ligase
  • Glutathione peroxidase
  • Glutathione S-transferase
  • Heme oxygenase
  • Keap1
  • MRP
  • NAD(P)H quinone oxidoreductase-1
  • Nrf2
  • Peroxiredoxin
  • Thioredoxin reductase

ASJC Scopus subject areas

  • Pharmacology

Cite this

Dual roles of Nrf2 in cancer. / Lau, Alexandria; Villeneuve, Nicole F.; Sun, Zheng; Wong, Pak Kin; Zhang, Donna.

In: Pharmacological Research, Vol. 58, No. 5-6, 11.2008, p. 262-270.

Research output: Contribution to journalArticle

Lau, Alexandria ; Villeneuve, Nicole F. ; Sun, Zheng ; Wong, Pak Kin ; Zhang, Donna. / Dual roles of Nrf2 in cancer. In: Pharmacological Research. 2008 ; Vol. 58, No. 5-6. pp. 262-270.
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