© 2006 The Japanese Biochemical Society.
JB Minireview--Polyamines |
Mammalian Polyamine Catabolism: A Therapeutic Target, a Pathological Problem, or Both?
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, Maryland, 21231, USA
* To whom correspondence should be addressed. Tel: +1-410-955-8580; Fax: +1-410-614-9884, E-Mail: rcasero{at}jhmi.edu
With the recent discovery of the polyamine catabolic enzyme spermine oxidase (SMO/PAOh1), the apparent complexity of the polyamine metabolic pathway has increased considerably. Alone or in combination with the two other known members of human polyamine catabolism, spermidine/spermine N1-acetyltransferase, and N1-acetylpolyamine oxidase (PAO), SMO/PAOh1 expression has the potential to alter polyamine homeostasis in response to normal cellular signals, drug treatment and environmental and/or cellular stressors. The activity of the oxidases producing toxic aldehydes and the reactive oxygen species (ROS) H2O2, suggest a mechanism by which these oxidases can be exploited as an antineoplastic drug target. However, inappropriate activation of the pathways may also lead to pathological outcomes, including DNA damage that can lead to cellular transformation. The most recent data suggest that the two polyamine catabolic pathways exhibit distinct properties and understanding these properties should aid in their exploitation for therapeutic and/or chemopreventive strategies.
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