Polyamine catabolism in carcinogenesis: Potential targets for chemotherapy and chemoprevention

Valentina Battaglia, Christina DeStefano Shields, Tracy Murray-Stewart, Robert A. Casero

Research output: Contribution to journalShort survey

Abstract

Polyamines, including spermine, spermidine, and the precursor diamine, putrescine, are naturally occurring polycationic alkylamines that are required for eukaryotic cell growth, differentiation, and survival. This absolute requirement for polyamines and the need to maintain intracellular levels within specific ranges require a highly regulated metabolic pathway primed for rapid changes in response to cellular growth signals, environmental changes, and stress. Although the polyamine metabolic pathway is strictly regulated in normal cells, dysregulation of polyamine metabolism is a frequent event in cancer. Recent studies suggest that the polyamine catabolic pathway may be involved in the etiology of some epithelial cancers. The catabolism of spermine to spermidine utilizes either the one-step enzymatic reaction of spermine oxidase (SMO) or the two-step process of spermidine/spermine N1- acetyltransferase (SSAT) coupled with the peroxisomal enzyme N 1-acetylpolyamine oxidase. Both catabolic pathways produce hydrogen peroxide and a reactive aldehyde that are capable of damaging DNA and other critical cellular components. The catabolic pathway also depletes the intracellular concentrations of spermidine and spermine, which are free radical scavengers. Consequently, the polyamine catabolic pathway in general and specifically SMO and SSAT provide exciting new targets for chemoprevention and/or chemotherapy.

Original languageEnglish (US)
Pages (from-to)511-519
Number of pages9
JournalAmino Acids
Volume46
Issue number3
DOIs
StatePublished - Mar 2014

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Keywords

  • Polyamines
  • Reactive oxygen species
  • Spermidine
  • Spermine
  • Spermine oxidase

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Organic Chemistry

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