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the role of nrf2 and cytoprotection in regulating chemotherapy resistance of human leukemia cellsnrf2和cytoprotection的作用在调节人类白血病细胞的化疗抵抗.pdf

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the role of nrf2 and cytoprotection in regulating chemotherapy resistance of human leukemia cellsnrf2和cytoprotection的作用在调节人类白血病细胞的化疗抵抗

Cancers 2011, 3, 1605-1621; doi:10.3390/cancers3021605 OPEN ACCESS cancers ISSN 2072-6694 /journal/cancers Review The Role of Nrf2 and Cytoprotection in Regulating Chemotherapy Resistance of Human Leukemia Cells Stuart A. Rushworth * and David J. MacEwan School of Pharmacy, University of East Anglia, Norwich NR4 7TJ, UK * Author to whom correspondence should be addressed; E-Mail: s.rushworth@uea.ac.uk; Tel.: +44 (0)1603 591802. 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 ch