Iron and Reactive Oxygen Species: Friends or Foes of Cancer Cells?
Laura M. Bystrom, Monica L. Guzman, and Stefano Rivella.
Antioxidants & Redox Signaling.
Online Ahead of Print: January 15, 2013
Online Ahead of Editing: December 2, 2012
1Department of Pediatrics—Hematology/Oncology, Weill Cornell Medical
College, New York, New York.
2Department of Pharmacology—Hematology Oncology, Weill Cornell Medical
College, New York, New York.
Address correspondence to:
Dr. Stefano Rivella
Department of Pediatrics—Hematology/Oncology
Weill Cornell Medical College
New York, NY 10021
E-mail: [email protected]
Dr. Monica L. Guzman
Department of Pharmacology in Medicine
Weill Cornell Medical College
New York, NY 10021
E-mail: [email protected]
Date of first submission to ARS Central, November 6, 2012
date of acceptance, December 1, 2012
ABSTRACT
Significance:
In this review, the dual nature of both iron and reactive oxygen
species (ROS) will be explored in normal and cancer cell metabolism.
Although iron and ROS play important roles in cellular homeostasis,
they may also contribute to carcinogenesis.
On the other hand, many studies have indicated that abrogation of iron
metabolism, elevation of ROS, or modification of redox regulatory
mechanisms in cancer cells, should be considered as therapeutic
approaches for cancer.
Recent Advances:
Drugs that target different aspects of iron metabolism may be
promising therapeutics for cancer.
The ability of iron chelators to cause iron depletion and/or elevate
ROS levels indicates that these types of compounds have more potential
as antitumor medicines than originally expected.
Other natural and synthetic compounds that target pathways involved in
ROS homeostasis also have potential value alone or in combination with
current chemotherapeutics.
Critical Issues:
Although ROS induction and iron depletion may be targets for cancer
therapies, the optimal therapeutic strategies have yet to be
identified.
This review highlights some of the research that strives to identify
such therapeutics.
Future Directions:
More studies are needed to better understand the role of iron and ROS
in carcinogenesis not only as cancer promoters, but also as cytotoxic
agents to cancer cells and cancer stem cells (CSCs).
Moreover, the structure–activity effects of iron chelators and other
compounds that increase ROS and/or disrupt iron metabolism need to be
further evaluated to assess the effectiveness and selectivity of these
compounds against both cancer and CSCs.

Antioxid. Redox Signal. 00, 000–000.

doi:10.1089/ars.2012.5014.

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