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The Role of Nrf2 and Cytoprotection in Regulating Chemotherapy Resistance of Human Leukemia Cells
School of Pharmacy, University of East Anglia, Norwich NR4 7TJ, UK
* Author to whom correspondence should be addressed.
Received: 10 January 2011; in revised form: 18 February 2011 / Accepted: 7 March 2011 / Published: 29 March 2011
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-κB (NF-κB) 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.
Keywords: leukemia; AML; CLL; apoptosis; transcription factor; Nrf2, antioxidant; HO-1; NQO1; glutathione; chemotherapy; NF-κB; acute myeloid leukemia
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MDPI and ACS Style
Rushworth, S.A.; MacEwan, D.J. The Role of Nrf2 and Cytoprotection in Regulating Chemotherapy Resistance of Human Leukemia Cells. Cancers 2011, 3, 1605-1621.
Rushworth SA, MacEwan DJ. The Role of Nrf2 and Cytoprotection in Regulating Chemotherapy Resistance of Human Leukemia Cells. Cancers. 2011; 3(2):1605-1621.
Rushworth, Stuart A.; MacEwan, David J. 2011. "The Role of Nrf2 and Cytoprotection in Regulating Chemotherapy Resistance of Human Leukemia Cells." Cancers 3, no. 2: 1605-1621.