title: Polyamine catabolism in carcinogenesis: potential targets for chemotherapy and chemoprevention.
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 N (1)-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.
authors.affiliation: The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Bunting Blaustein Bldg., Room 551, 1650 Orleans Street, Baltimore, MD, 21287, USA.
authors.forename: Valentina
authors.initials: V
authors.lastname: Battaglia
authors.forename: Christina
authors.initials: C
authors.lastname: DeStefano Shields
authors.forename: Tracy
authors.initials: T
authors.lastname: Murray-Stewart
authors.forename: Robert A
authors.initials: RA
authors.lastname: Casero
mesh_terms: D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D063646:Carcinogenesis; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D011073:Polyamines / Q000378:metabolism*
chemical_list: D000447:Aldehydes; D011073:Polyamines; D006861:Hydrogen Peroxide