Nrf2 – Two Faces of Antioxidant System Regulation

Česká verzia

Authors: M. Pastorek; P. Müller; B. Vojtěšek
Authors place of work: Regionální centrum aplikované molekulární onkologie, Masarykův onkologický ústav, Brno
Published in the journal: Klin Onkol 2015; 28(Supplementum 2): 26-31
doi: https://doi.org/10.14735/amko20152S26

Summary

One of the most prominent defense mechanisms of cells undergoing stress is the Nrf2-Keap1 signaling pathway. After exposure to either carcinogens or toxic compounds inducing oxidative stress, attacked cells react by release of Keap1 from the Nrf2-Keap1 complex. Freeing Nrf2 from the complex allows its translocation into the nucleus, thus enabling start of the transcriptional program of cytoprotective genes. Therefore, induction of Nrf2 by chemopreventive compounds may show potential in cancer prevention. But while it protects normal cells, increased activity of Nrf2 signaling pathway also facilitates cancer progression and protects neoplastic cells from therapeutic agents. Increased expression and subsequent accumulation of Nrf2 contributes to acquired drug resistance and is often associated with worse prognosis. Knowing ‘both faces’ of Nrf2 signaling pathway is thus relevant not only for basic research but has also substantial clinical implications.

Key words:
Nrf2 – Keap1 – antioxidant – drug resistance – chemoprevention

This study was supported by European Re-gional Development Fund and the State Budget of the Czech Republic (RECAMO CZ.1.05//2.1.00/03.0101), MEYS – NPS I – LO1413, MH CZ –DRO (MMCI, 00209805) and by BBMRI_CZ (LM2010004).

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE “uniform requirements” for biomedical papers.

Submitted:
9. 4. 2015

Accepted:
15. 6. 2015

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