Next Article in Journal
Predictive and Prognostic Factors in Colorectal Cancer: A Personalized Approach
Next Article in Special Issue
Targeting the Anti-Apoptotic Protein c-FLIP for Cancer Therapy
Previous Article in Journal
Role of Surgery in Stages II and III Pediatric Abdominal Non-Hodgkin Lymphoma: A 5-Years Experience
Previous Article in Special Issue
To Die or to Survive, a Fatal Question for the Destiny of Prostate Cancer Cells after Androgen Deprivation Therapy
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

*  and
School of Pharmacy, University of East Anglia, Norwich NR4 7TJ, UK
* Author to whom correspondence should be addressed.
Received: 10 January 2011 / Revised: 18 February 2011 / Accepted: 7 March 2011 / Published: 29 March 2011
(This article belongs to the Special Issue Cell Death and Cancer)
View Full-Text   |   Download PDF [309 KB, 30 March 2011; original version 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 leukemia; AML; CLL; apoptosis; transcription factor; Nrf2, antioxidant; HO-1; NQO1; glutathione; chemotherapy; NF-κB; acute myeloid leukemia
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).
SciFeed

Share & Cite This Article

Further Mendeley | CiteULike
Export to BibTeX |
EndNote |
RIS
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.

View more citation formats

Related Articles

Article Metrics

For more information on the journal, click here

Comments

[Return to top]
Cancers EISSN 2072-6694 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert