Nrf2 is a transcription factor that regulates a cellular defense response which promotes cell survival under detrimental environments, such as oxidative stress. Nrf2 has recently emerged as an important contributor to chemoresistance, a major obstacle limiting the successful treatment of cancer patients.

Donna Zhang and co-workers, University of Arizona, USA, have discovered an antioxidant compound that inhibits the Nrf2 defense response mechanism. The quassinoid compound, brusatol, was isolated from the fruit of the Brucea javanica tree.

Zhang’s team showed that brusatol can sensitize a broad spectrum of cancer cells and A549 xenografts to cisplatin and other chemotherapeutic drugs. When brusatol was used in combination with cisplatin, there was an increase in cell death, reduced cell proliferation, and a reduction in tumor growth compared to cisplatin treatment alone.

• Brusatol enhances the efficacy of chemotherapy by inhibiting the Nrf2-mediated defense mechanism
  D. Ren, N. F. Villeneuve, T. Jiang, T. Wu, A. Lau, H. A. Toppin, D. D. Zhang,
  Proc. Natl. Acad. Sci. 2011, 108(4), 1433-1438.
  DOI: 10.1073/pnas.1014275108