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Polyamine catabolism: target for antiproliferative therapies in animals and stress tolerance strategies in plants

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Abstract

Metabolism of polyamines spermidine and spermine, and their diamine precursor, putrescine, has been a target for antineoplastic therapy since these naturally occurring alkyl amines were found essential for normal mammalian cell growth. Intracellular polyamine concentrations are maintained at a cell type-specific set point through the coordinated and highly regulated interplay between biosynthesis, transport, and catabolism. A correlation between regulation of cell proliferation and polyamine metabolism is described. In particular, polyamine catabolism involves copper-containing amine oxidases and FAD-dependent polyamine oxidases. Several studies showed an important role of these enzymes in several developmental and disease-related processes in both animals and plants through a control on polyamine homeostasis in response to normal cellular signals, drug treatment, environmental and/or cellular stressors. The production of toxic aldehydes and reactive oxygen species, H2O2 in particular, by these oxidases using extracellular and intracellular polyamines as substrates, suggests a mechanism by which the oxidases can be exploited as antineoplastic drug targets. This minireview summarizes recent advances on the physiological roles of polyamine catabolism in animals and plants in an attempt to highlight differences and similarities that may contribute to determine in detail the underlined mechanisms involved. This information could be useful in evaluating the possibility of this metabolic pathway as a target for new antiproliferative therapies in animals and stress tolerance strategies in plants.

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Abbreviations

ABA:

Abscisic acid

ADC:

Arginine decarboxylase

ALDH:

Aldehyde dehydrogenase

AMADH:

Aminoaldehyde dehydrogenase

APAO:

N 1-acetylpolyamine oxidase

ATAO:

Arabidopsis thaliana CuAO

AtPAO:

Arabidopsis thaliana PAO

BENSpm:

Bis(ethyl)norspermine

BSAO:

Bovine serum amine oxidase

CHO:

Chinese hamster ovary

CPENSpm:

N 1-ethyl-N 11-[(cyclopropyl)methyl]-4,8-diazaundecane

CuAO:

Copper amine oxidase

Dap:

1,3-diaminopropane

DFMO:

Difluoromethylornithine

DX:

Doxorubicin-resistant

eIF5A:

Eukaryotic translation initiation factor 5A

FBS:

Fetal bovine serum

GABA:

γ-aminobutyric acid

HO·:

Hydroxyl radical

HR:

Hypersensitive response

JA:

Jasmonic acid

MDR:

Multidrug-resistant

NSAIDS:

Non-steroidal anti-inflammatory drugs

ODC:

Ornithine decarboxylase

PAO:

Polyamine oxidase

PBS-BSA:

Phosphate buffered saline-bovin serum albumin

PC-Acro:

Protein conjugated acrolein

PCD:

Programmed cell death

P-gp:

P-glycoprotein

Put:

Putrescine

ROS:

Reactive oxygen species

SA:

Salicylic acid

SAMDC:

S-adenosylmethionine decarboxylase

SMO:

Spermine oxidase

Spd:

Spermidine

SPDS:

Spd synthase

Spm:

Spermine

SPMS:

Spm synthase

SSAT:

Spd/Spm N 1-acetyltransferase

Ther-Spm:

Thermospermine

TMV:

Tobacco mosaic virus

TNFα:

Tumor-necrosis factor α

TPQ:

2,4,5-trihydroxyphenylalaninequinone

ZmPAO:

Maize PAO

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Acknowledgments

This work was partially supported by the Italian MIUR (Ministero dell’Istruzione, dell’Università e della Ricerca), by Istituto Superiore di Sanità “Project Italy-USA”, by Istituto Pasteur-Fondazione Cenci Bolognetti and by funds MIUR-PRIN (Cofin). Thanks are due to Fondazione ‘Enrico ed Enrica Sovena’ for the scholarships given to Nikenza Viceconte and Stefania Saccoccio for supporting their Ph.D.

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Correspondence to Enzo Agostinelli.

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Tavladoraki, P., Cona, A., Federico, R. et al. Polyamine catabolism: target for antiproliferative therapies in animals and stress tolerance strategies in plants. Amino Acids 42, 411–426 (2012). https://doi.org/10.1007/s00726-011-1012-1

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