Targeting polyamine metabolism for cancer therapy and prevention.
The chemically simple, biologically complex eukaryotic polyamines, spermidine and spermine, are positively charged alkylamines involved in many crucial cellular processes. Along with their diamine precursor putrescine, their normally high intracellular concentrations require fine attenuation by multiple regulatory mechanisms to keep these essential molecules within strict physiologic ranges. Since the metabolism of and requirement for polyamines are frequently dysregulated in neoplastic disease, the metabolic pathway and functions of polyamines provide rational drug targets; however, these targets have been difficult to exploit for chemotherapy. It is the goal of this article to review the latest findings in the field that demonstrate the potential utility of targeting the metabolism and function of polyamines as strategies for both chemotherapy and, possibly more importantly, chemoprevention.
The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 1650 Orleans Street, Bunting, Blaustein Building, Room 551, Baltimore, MD 21287, USA.
Tracy R
TR
Murray-Stewart
Department of Drug Discovery and Biomedical Sciences, Medical University of South Carolina, Charleston, SC 29425, USA.
Patrick M
PM
Woster
The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 1650 Orleans Street, Bunting, Blaustein Building, Room 551, Baltimore, MD 21287, USA.
Robert A
RA
Casero
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology; D001692:Biological Transport; D004359:Drug Therapy, Combination; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control*; D011073:Polyamines / Q000378:metabolism*
D000970:Antineoplastic Agents; D011073:Polyamines
cancer therapy; chemoprevention; epigenetics; polyamines; reactive oxygen species; spermine oxidase
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