Cancers 2011, 3(2), 1605-1621; doi:10.3390/cancers3021605
Review

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

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Received: 10 January 2011; in revised form: 18 February 2011 / Accepted: 7 March 2011 / Published: 29 March 2011
(This article belongs to the Special Issue Cell Death and Cancer)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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.

AMA Style

Rushworth SA, MacEwan DJ. The Role of Nrf2 and Cytoprotection in Regulating Chemotherapy Resistance of Human Leukemia Cells. Cancers. 2011; 3(2):1605-1621.

Chicago/Turabian Style

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.

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