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Amino Acids

, Volume 38, Issue 2, pp 393–403 | Cite as

Polyamines: fundamental characters in chemistry and biology

  • E. Agostinelli
  • M. P. M. Marques
  • R. Calheiros
  • F. P. S. C. Gil
  • G. Tempera
  • N. Viceconte
  • V. Battaglia
  • S. Grancara
  • A. Toninello
Review Article

Abstract

Polyamines are small cationic molecules required for cellular proliferation and are detected at higher concentrations in most tumour tissues, compared to normal tissues. Agmatine (AGM), a biogenic amine, is able to arrest proliferation in cell lines by depleting intracellular polyamine levels. It enters mammalian cells via the polyamine transport system. Agmatine is able to induce oxidative stress in mitochondria at low concentrations (10 or 100 μM), while at higher concentrations (e.g. 1–2 mM) it does not affect mitochondrial respiration and is ineffective in inducing any oxidative stress. As this effect is strictly correlated with the mitochondrial permeability transition induction and the triggering of the pro-apoptotic pathway, AGM may be considered as a regulator of this type of cell death. Furthermore, polyamine transport is positively correlated with the rate of cellular proliferation. By increasing the expression of antizyme, a protein that inhibits polyamine biosynthesis and transport, AGM also exhibits a regulatory effect on cell proliferation. Methylglyoxal bis(guanylhydrazone) (MGBG), a competitive inhibitor of S-adenosyl-l-methionine decarboxylase, displaying anticancer activity, is a structural analogue of the natural polyamine spermidine. MGBG has been extensively studied, preclinically as well as clinically, and its anticancer activity has been attributed to the inhibition of polyamine biosynthesis and also to its effect on mitochondrial function. Numerous findings have suggested that MGBG might be used as a chemotherapeutic agent against cancer.

Keywords

Biogenic polyamines Quantum mechanical calculations Agmatine MGBG Structure–activity relationships Mitochondria 

Abbreviations

ADC

Arginine decarboxylase

AGM

Agmatine (4-(aminobutyl)guanidine)

AO-Agm

N-(3-aminoxy-propyl)-guanidin

BSAO

Bovine serum amine oxidase

DFMO

(d, l)-2-(difluoromethyl)ornithine

EMT

Extraneuronal monoamine transporter

GAPA

N-(3-aminopropoxy)guanidine

INS

Inelastic neutron scattering

IR

Infrared spectroscopy

MDR

Multidrug resistant

MGBG

Methylglyoxal bis(guanylhydrazone)

MPT

Mitochondrial permeability transition

NGPG

N-(3-guanidino-propoxy)guanidine

OCT2

Organic cation transporter 2

ODC

Ornithine decarboxylase

PAs

Polyamines

RLM

Rat liver mitochondria

ROS

Reactive oxygen species

SAMDC

S-adenosyl-l-methionine decarboxylase

SAR’s

Structure–activity relationships

SSAT

Spermidine/spermine N-acetyltransferase

Notes

Acknowledgments

MPMM acknowledges financial support from the Portuguese Foundation for Science and Technology (FCT)—Project PTDC/QUI/66701/2006 (co-financed by the European Community fund FEDER). Thanks are due to the Italian MIUR (Ministero dell’Istruzione, dell’Università e della Ricerca) and MIUR-PRIN-Cofin (EA). Thanks are due to ‘Fondazione Sovena’ for the scholarship given to Nikenza Viceconte for supporting her Ph.D.

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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • E. Agostinelli
    • 1
    • 2
  • M. P. M. Marques
    • 3
  • R. Calheiros
    • 3
  • F. P. S. C. Gil
    • 4
  • G. Tempera
    • 1
  • N. Viceconte
    • 1
  • V. Battaglia
    • 5
  • S. Grancara
    • 5
  • A. Toninello
    • 5
  1. 1.Department of Biochemical SciencesBiology and Molecular Pathology Institutes, SAPIENZA University of Rome and CNRRomeItaly
  2. 2.Department of Biochemical SciencesSAPIENZA University of RomeRomeItaly
  3. 3.Molecular Physical-ChemistryR&D Unit University of CoimbraCoimbraPortugal
  4. 4.CEMDRX, Physics DepartmentUniversity of CoimbraCoimbraPortugal
  5. 5.Department of Biological ChemistryUniversity of PaduaPaduaItaly

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