TY - JOUR
T1 - Polyamine catabolism in carcinogenesis
T2 - Potential targets for chemotherapy and chemoprevention
AU - Battaglia, Valentina
AU - DeStefano Shields, Christina
AU - Murray-Stewart, Tracy
AU - Casero, Robert A.
N1 - Funding Information:
Portions of the work described in this manuscript were supported by the NIEHS T32 training grant ES07141 and NCI grants CA51085 and CA98454.
PY - 2014/3
Y1 - 2014/3
N2 - 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.
AB - 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.
KW - Polyamines
KW - Reactive oxygen species
KW - Spermidine
KW - Spermine
KW - Spermine oxidase
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U2 - 10.1007/s00726-013-1529-6
DO - 10.1007/s00726-013-1529-6
M3 - Short survey
C2 - 23771789
AN - SCOPUS:84896316188
SN - 0939-4451
VL - 46
SP - 511
EP - 519
JO - Amino Acids
JF - Amino Acids
IS - 3
ER -