The Role of Nrf2 and Cytoprotection in Regulating Chemotherapy Resistance of Human Leukemia Cells

Stuart Rushworth, David J Macewan

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

The Nrf2 anti-oxidant response element (ARE) pathway plays an important role in regulating cellular anti-oxidants. Under normal cellular conditions Nrf2 can be described as an anti-tumor molecule due to its induction of cytoprotective genes which protect cells from electrophile and oxidative damage. However in cancerous cells, Nrf2 takes on a pro-tumoral identity as the same cytoprotective genes can enhance resistance of those cancer cells to chemotherapeutic drugs. Such Nrf2-regulated cytoprotective genes include heme oxygenase-1 (HO-1), which has been shown to protect human leukemia cells from apoptotic signals. Moreover, a relationship between Nrf2 and the nuclear factor-?B (NF-?B) signaling pathway has been recently identified, and is now recognized as an important cross-talk mechanism by which Nrf2 can overcome apoptosis and provide cells with reduced sensitivity towards chemotherapeutic agents. In recent years a number of important research papers have highlighted the role of Nrf2 in providing protection against both current and new chemotherapeutic drugs in blood cancer. This review will provide a synopsis of these research papers with an aim to carefully consider if targeting Nrf2 in combination with current or new chemotherapeutics is a viable strategy in the more effective treatment of blood cancers.
Original languageEnglish
Pages (from-to)1605-1621
Number of pages17
JournalCancers
Volume3
Issue number2
DOIs
Publication statusPublished - 29 Mar 2011

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