Pharmacological Applications of Nrf2 Inhibitors as Potential Antineoplastic Drugs

Int J Mol Sci. 2019 Apr 24;20(8):2025. doi: 10.3390/ijms20082025.

Abstract

Oxidative stress (OS) is associated with many diseases ranging from cancer to neurodegenerative disorders. Nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) is one of the most effective cytoprotective controller against OS. Modulation of Nrf2 pathway constitutes a remarkable strategy in the antineoplastic treatments. A big number of Nrf2-antioxidant response element activators have been screened for use as chemo-preventive drugs in OS associated diseases like cancer even though activation of Nrf2 happens in a variety of cancers. Research proved that hyperactivation of the Nrf2 pathway produces a situation that helps the survival of normal as well as malignant cells, protecting them against OS, anticancer drugs, and radiotherapy. In this review, the modulation of the Nrf2 pathway, anticancer activity and challenges associated with the development of an Nrf2-based anti-cancer treatment approaches are discussed.

Keywords: Nrf2 inhibitors; antineoplastic drugs; cancer; cancer chemoprevention and therapy; chemoresistance.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Drug Development
  • Humans
  • NF-E2-Related Factor 2 / antagonists & inhibitors*
  • NF-E2-Related Factor 2 / metabolism
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Oxidative Stress / drug effects
  • Signal Transduction / drug effects*

Substances

  • Antineoplastic Agents
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human