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


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.


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



Arginine decarboxylase


Agmatine (4-(aminobutyl)guanidine)




Bovine serum amine oxidase


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


Extraneuronal monoamine transporter




Inelastic neutron scattering


Infrared spectroscopy


Multidrug resistant


Methylglyoxal bis(guanylhydrazone)


Mitochondrial permeability transition




Organic cation transporter 2


Ornithine decarboxylase




Rat liver mitochondria


Reactive oxygen species


S-adenosyl-l-methionine decarboxylase


Structure–activity relationships


Spermidine/spermine N-acetyltransferase



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.


  1. Agostinelli E, Arancia G, Dalla Vedova L, Belli F, Marra M, Salvi M, Toninello A (2004) The biological functions of polyamine oxidation products by amine oxidases: perspectives of clinical applications. Amino Acids 27:347–358CrossRefPubMedGoogle Scholar
  2. Agostinelli E, Belli F, Molinari A, Condello M, Palmigiani P, Dalla Vedova L, Marra M, Seiler N, Arancia G (2006) Toxicity of enzymatic oxidation products of spermine to human melanoma cells (M14): sensitisation by heat and MDL 72527. Biochim Biophys Acta 1763:1040–1050CrossRefPubMedGoogle Scholar
  3. Agostinelli E, Tempera G, Molinari A, Salvi M, Battaglia V, Toninello A, Arancia G (2007) The physiological role of biogenic amines redox reactions in mitochondria. New perspectives in cancer therapy. Amino Acids 33:175–187CrossRefPubMedGoogle Scholar
  4. Agostinelli E, Condello M, Molinari A, Tempera G, Viceconte N, Arancia G (2009) Cytotoxicity of spermine oxidation products to multidrug resistant melanoma cells (M14 ADR2): sensitisation by MDL 72527, a lysosomotropic compound. Int J Oncol 35:485–498CrossRefPubMedGoogle Scholar
  5. Amado AM, Otero JC, Marques MPM, Batista de Carvalho LAE (2004) Spectroscopic and theoretical studies on solid 1, 2-ethylenediamine dihydrochloride salt. Chem Phys Chem 5:1837–1847PubMedGoogle Scholar
  6. Amorim da Costa AM, Marques MPM, Batista de Carvalho LAE (2002) The carbon-hydrogen stretching region of the Raman Spectra of 1, 6-hexane-diamine: N-deuteration, ionization and temperature effects. J Vib Spec 29:61–67CrossRefGoogle Scholar
  7. Amorim da Costa AM, Marques MPM, Batista de Carvalho LAE (2003) Raman Spectra of putrescine, spermidine and spermine polyamines and their N-deuterated and N-ionised derivatives. J Raman Spec 34:357–366CrossRefGoogle Scholar
  8. Amorim da Costa AM, Batista de Carvalho LAE, Marques MPM (2004) Intra- vs. interchain interactions in α, ω-polyamines: a Raman Spectroscopy study. J Vib Spec 35:165–171CrossRefGoogle Scholar
  9. Averill-Bates DA, Cherif A, Agostinelli E, Tanel A, Fortier G (2005) Anti-tumoral effect of native and immobilized bovine serum amine oxidase in a mouse melanoma model. Biochem Pharmacol 69:1693–1704CrossRefPubMedGoogle Scholar
  10. Averill-Bates DA, Ke Q, Tanel A, Roy J, Fortier G, Agostinelli E (2008) Mechanism of cell death induced by spermine and amine oxidase in mouse melanoma cells. Int J Oncol 32:79–88PubMedGoogle Scholar
  11. Babal P, Ruchko M, Campbell CC, Gilmour SP, Mitchell JL, Olson JW, Gillespie MN (2001) Regulation of ornithine decarboxylase activity and polyamine transport by agmatine in rat pulmonary artery endothelial cells. J Pharmacol Exp Ther 296:372–377PubMedGoogle Scholar
  12. Bachrach U (2005) Naturally occurring polyamines: interaction with macromolecules. Curr Protein Pept Sci 6:559–566CrossRefPubMedGoogle Scholar
  13. Batista de Carvalho LAE, Lourenço LE, Marques MPM (1999) Conformational study of 1,2-diaminoethane by combined ab initio MO calculations and Raman spectroscopy. J Mol Struct 482–483: 639–646, and refs. thereinGoogle Scholar
  14. Battaglia V, Rossi CA, Colombatto S, Grillo MA, Toninello A (2007) Different behaviour of agmatine in liver mitochondria: inducer of oxidative stress or scavenger of reactive oxygen species? Biochim Biophys Acta 1768:1147–1153CrossRefPubMedGoogle Scholar
  15. Cabella C, Gardini G, Corpillo D, Testore G, Bedino S, Solinas SP, Cravanzola C, Vargiu C, Grillo MA, Colombatto S (2001) Transport and metabolism of agmatine in rat hepatocyte cultures. Eur J Biochem 268:940–947CrossRefPubMedGoogle Scholar
  16. Cardillo S, Iuliis AD, Battaglia V, Toninello A, Stevanato R, Vianello F (2009) Novel copper amine oxidase activity from rat liver mitochondria matrix. Arch Biochem Biophys 485:97–101CrossRefPubMedGoogle Scholar
  17. Carew JS, Nawrocki ST, Reddy VK, Bush D, Rehg JE, Goodwin A, Houghton JA, Casero RA, Marton LJ, Cleveland JL (2008) The novel polyamine analogue CGC-11093 enhances the antimyeloma activity of bortezomib. Cancer Res 68:4783–4790CrossRefPubMedGoogle Scholar
  18. Casero RA, Marton LJ (2007) Targeting polyamine metabolism and function in cancer and other hyperproliferative diseases. Nat Rev Drug Discov 6:373–390CrossRefPubMedGoogle Scholar
  19. Dalla Via L, Di Noto V, Siliprandi D, Toninello A (1996) Spermidine binding to liver mitochondria. Biochim Biophys Acta 1284:247–252CrossRefPubMedGoogle Scholar
  20. Dudkowska M, Lai J, Gardini G, Stachurska A, Grzelakowska-Sztabert B, Colombatto S, Manteuffel-Cymborowska M (2003) Agmatine modulates the in vivo biosynthesis and interconversion of polyamines and cell proliferation. Biochim Biophys Acta 1619:159–166PubMedGoogle Scholar
  21. Fiuza SM, Amado AM, Oliveira PJ, Sardão VA, Batista de Carvalho LAE, Marques MPM (2006) Pt(II) vs Pd(II) Polyamine complexes as new anticancer drugs: a structure-activity study. Lett Drug Des Dev 3:149–151CrossRefGoogle Scholar
  22. Fogel-Petrovic M, Vujcic S, Miller J, Porter CW (1996) Differential post-transcriptional control of ornithine decarboxylase and spermidine-spermine N1-acetyltransferase by polyamines. FEBS Lett 391:89–94CrossRefPubMedGoogle Scholar
  23. Fogel-Petrovic M, Kramer DL, Vujcic S, Miller J, Mcmanis JS, Bergeron RJ, Porter CW (1997) Structural basis for differential induction of spermidine/spermine N1-acetyltransferase activity by novel spermine analogs. Mol Pharmacol 52:69–74PubMedGoogle Scholar
  24. Gardini G, Cabella C, Cravanzola C, Vargiu C, Belliardo S, Testore G, Solinas SP, Toninello A, Grillo MA, Colombatto S (2001) Agmatine induces apoptosis in rat hepatocyte cultures. J Hepatol 35:482–489CrossRefPubMedGoogle Scholar
  25. Gerner EW, Meyskens FL Jr (2004) Polyamines and cancer: old molecules, new understanding. Nat Rev Cancer 4:781–792CrossRefPubMedGoogle Scholar
  26. Gerner EW, Meyskens FL Jr, Goldschmid S, Lance P, Pelot D (2007) Rationale for, and design of, a clinical trial targeting polyamine metabolism for colon cancer chemoprevention. Amino Acids 33:189–195CrossRefPubMedGoogle Scholar
  27. Goldenthal MJ, Marin-Garcia J (2004) Mitochondrial signaling pathways: a receiver/integrator organelle. Mol Cell Biochem 262:1–16CrossRefPubMedGoogle Scholar
  28. Grillo MA, Colombatto S (2004) Metabolism and function in animal tissues of agmatine, a biogenic amine formed from arginine. Amino Acids 26:3–8CrossRefPubMedGoogle Scholar
  29. Grillo MA, Battaglia V, Colombatto S, Rossi CA, Simonian AR, Salvi M, Khomutov AR, Toninello A (2007) Inhibition of agmatine transport in liver mitochondria by new charge-deficient agmatine analogues. Biochem Soc Trans 35:401–404CrossRefPubMedGoogle Scholar
  30. Grundemann D, Hahne C, Berkels R, Schomig E (2003) Agmatine is efficiently transported by non-neuronal monoamine transporters extraneuronal monoamine transporter (EMT) and organic cation transporter 2 (OCT2). J Pharmacol Exp Ther 304:810–817CrossRefPubMedGoogle Scholar
  31. Gupta R, Krause-Ihle T, Bergmann B, Muller IB, Khomutov AR, Muller S, Walter RD, Luersen K (2005) 3-Aminooxy-1-aminopropane and derivatives have an antiproliferative effect on cultured Plasmodium falciparum by decreasing intracellular polyamine concentrations. Antimicrob Agents Chemother 49:2857–2864CrossRefPubMedGoogle Scholar
  32. Ha HC, Sirisoma NS, Kuppusamy P, Zweier JL, Woster PM, Casero RA (1998) The natural polyamine spermine functions directly as a free radical scavenger. Proc Natl Acad Sci USA 95:11140–11145CrossRefPubMedGoogle Scholar
  33. Harris A, Qu Y, Farrell N (2005) Unique cooperative binding interaction observed between a minor groove binding Pt antitumor agent and Hoechst dye 33258. Inorg Chem 44:1196–1198CrossRefPubMedGoogle Scholar
  34. Harris AL, Ryan JJ, Farrell N (2006) Biological consequences of trinuclear platinum complexes: comparison of [[trans-PtCl(NH3)2]2mu-(trans-Pt(NH3)2(H2N(CH2)6-NH2)2)]4+ (BBR 3464) with its non covalent congeners. Mol Pharmacol 69:666–672CrossRefPubMedGoogle Scholar
  35. Heby O, Persson L (1990) Molecular genetics of polyamine synthesis in eukaryotic cells. Trends Biochem Sci 15:153–158CrossRefPubMedGoogle Scholar
  36. Higashi K, Yoshida K, Nishimura K, Momiyama E, Kashiwagi K, Matsufuji S, Shirahata A, Igarashi K (2004) Structural and functional relationship among diamines in terms of inhibition of cell growth. J Biochem 136:533–539CrossRefPubMedGoogle Scholar
  37. Huang Y, Keen JC, Pledgie A, Marton LJ, Zhu T, Sukumar A, Park BH, Blair B, Brenner K, Casero RA, Davidson NE (2006) Polyamine analogues down-regulate estrogen receptor alpha expression in human breast cancer cells. J Biol Chem 281:19055–19063CrossRefPubMedGoogle Scholar
  38. Ichimura S, Hamana K, Nenoi M (1998) Significant increases in the steady states of putrescine and spermidine/spermine N1-acetyltransferase mRNA in HeLa cells accompanied by growth arrest. Biochem Biophys Res Commun 243:518–521CrossRefPubMedGoogle Scholar
  39. Jänne J, Alhonen L, Leinonen P (1991) Polyamines: from molecular biology to clinical applications. Ann Med 23:241–259CrossRefPubMedGoogle Scholar
  40. Komeda S, Moulaei T, Woods KK, Chikuma M, Farrell NP, Williams LD (2006) A third mode of DNA binding: phosphate clamps by a polynuclear platinum complex. J Am Chem Soc 128:16092–16103CrossRefPubMedGoogle Scholar
  41. Li G, Regunathan S, Barrow CJ, Eshraghi J, Cooper R, Reis DJ (1994) Agmatine: an endogenous clonidine-displacing substance in the brain. Science 263:966–969CrossRefPubMedGoogle Scholar
  42. Liu Q, Qu Y, Van Antwerpen R, Farrell N (2006) Mechanism of the membrane interaction of polynuclear platinum anticancer agents. Implications for cellular uptake. Biochemistry 45:4248–4256CrossRefPubMedGoogle Scholar
  43. Lortie MJ, Novotny WF, Pederson OW, Vallon V, Malvey K, Mendonca M, Satriano J, Insel P, Thomson SC, Blantz RC (1996) Agmatine, a bioactive metabolite of arginine. Production, degradation, and functional effects in the kidney of the rat. J Clin Invest 97:413–420CrossRefPubMedGoogle Scholar
  44. Manni A, Washington S, Hu X, Griffith JW, Bruggeman R, Demers LM, Mauger D, Verderame MF (2006) Effects of polyamine synthesis inhibitors on primary tumor features and metastatic capacity of human breast cancer cells. Clin Exp Metastasis 22:255–263CrossRefGoogle Scholar
  45. Marques MPM, Batista de Carvalho LAE (2000) COST 917: Biogenically active amines in food. In: Morgan DML, White A, Sánchez-Jiménez F, Bardocz S (eds) Theoretical approach to the conformational preferences of putrescine. European commission, Luxembourg, p 122Google Scholar
  46. Marques MPM, Batista de Carvalho LAE (2007) Vibrational spectroscopy studies on linear polyamines. Biochem Soc Trans 35:374–380CrossRefPubMedGoogle Scholar
  47. Marques MPM, Batista de Carvalho LAE, Tomkinson J (2002a) Study of biogenic and α, ω-polyamines by combined inelastic neutron scattering and Raman spectroscopies, and ab initio MO calculations. J Phys Chem A 106:2473–2482CrossRefGoogle Scholar
  48. Marques MPM, Girão T, Pedroso de Lima MC, Gameiro A, Pereira E, Garcia P (2002b) Cytotoxic effects of metal complexes of biogenic polyamines. I–Platinum(II) spermidine compounds: Prediction of their antitumour activity. Biochim Biophys Acta 1589:63–70CrossRefPubMedGoogle Scholar
  49. Marques MPM, Batista de Carvalho LAE, Tomkinson J (2006) Transverse acoustic modes of biogenic and alpha, omega-polyamines: a study by inelastic neutron scattering and Raman spectroscopies coupled to DFT calculations. J Phys Chem 110:12947–12954Google Scholar
  50. Marques MPM, Borges F, Amorim da Costa AM, Batista de Carvalho LAE (2007) Vibrational spectroscopy studies on biologically relevant molecules. From anticancer agents to drugs of abuse. In: Kneip K, Aroca R, Kneipp H, Wentrup-Byrne E (eds) ACS symposium $eries no. 963—new approaches in biomedical spectroscopy. American Chemical Society, Washington, DC, pp 338–363CrossRefGoogle Scholar
  51. Marques MPM, Gil FPSC, Calheiros R, Battaglia V, Brunati AM, Toninello A (2008) Biological activity of antitumoural MGBG—the structural variable. Amino Acids 34:555–564CrossRefPubMedGoogle Scholar
  52. Marton LJ, Pegg AE (1995) Polyamines as targets for therapeutic intervention. Annu Rev Pharmacol Toxicol 35:55–91CrossRefPubMedGoogle Scholar
  53. N’soukpo-Kossi CN, Ouameur AA, Thomas T, Shirahata A, Thomas TJ, Tajmir-Riahi HA (2008) DNA interaction with antitumor polyamine analogues: a comparison with biogenic polyamines. Biomacromolecules 9:2712–2718CrossRefGoogle Scholar
  54. Nakaike S, Kashiwagi K, Terao K, Iio K, Igarashi K (1988) Combined use of alpha-difluoromethylornithine and an inhibitor of S-adenosylmethionine decarboxylase in mice bearing P388 leukaemia or Lewis lung carcinoma. Jpn J Cancer Res 79:501–508PubMedGoogle Scholar
  55. Nasizadeh S, Myhre L, Thiman L, Alm K, Oredsson S, Persson L (2005) Importance of polyamines in cell cycle kinetics as studied in a transgenic system. Exp Cell Res 308:254–264CrossRefPubMedGoogle Scholar
  56. Ouameur AA, Tajmir-Riahi HA (2004) Structural analysis of DNA interactions with biogenic polyamines and cobalt(III)hexamine studied by Fourier transform infrared and capillary electrophoresis. J Biol Chem 279:42041–42054CrossRefPubMedGoogle Scholar
  57. Patel MM, Anchoroquy TJ (2006) Ability of spermine to differentiate between DNA sequences—preferential stabilization of A-tracts. Biophys Chem 122:5–15CrossRefPubMedGoogle Scholar
  58. Pegg AE (2008) Spermidine/spermine-N(1)-acetyltransferase: a key metabolic regulator. Am J Physiol Endocrinol Metab 294:E995–E1010CrossRefPubMedGoogle Scholar
  59. Pegg AE, Feith DJ (2007) Polyamines and neoplastic growth. Biochem Soc Trans 35:295–299CrossRefPubMedGoogle Scholar
  60. Pezzato E, Battaglia V, Brunati AM, Agostinelli E, Toninello A (2009) Ca2+-independent effects of spermine on pyruvate dehydrogenase complex activity in energized rat liver mitochondria incubated in the absence of exogenous Ca2+ and Mg2+. Amino Acids 36:449–456CrossRefPubMedGoogle Scholar
  61. Pleshkewych A, Kramer DL, Kelly E, Porter CW (1980) Independence of drug action on mitochondria and polyamines in L1210 leukemia cells treated with methylglyoxal-bis(guanylhydrazone). Cancer Res 40:4533–4540PubMedGoogle Scholar
  62. Pratesi G, Perego P, Polizzi D, Righetti SC, Supino R, Caserini C, Manzotti C, Giuliani FC, Pezzoni G, Tognella S, Spinelli S, Farrell N, Zunino F (1999) A novel charged trinuclear platinum complex effective against cisplatin-resistant tumours: hypersensitivity of p53-mutant human tumour xenografts. Br J Cancer 80:1912–1919CrossRefPubMedGoogle Scholar
  63. Qu Y, Rauter H, Soares-Fontes AP, Bandarage R, Kelland LR, Farrell N (2000) Synthesis, characterization and cytotoxicity of trifunctional dinuclear platinum complexes: comparison of effects of geometry and polyfunctionality on biological activity. J Med Chem 43:89–92Google Scholar
  64. Raasch W, Schafer U, Chun J, Dominiak P (2001) Biological significance of agmatine, an endogenous ligand at imidazoline binding sites. Br J Pharmacol 133:755–780CrossRefPubMedGoogle Scholar
  65. Regenass U, Caravatti G, Mett H, Stanek J, Schneider P, Muller M (1992) New S-adenosylmethionine decarboxylase inhibitors with potent antitumor activity. Cancer Res 52:4712–4718PubMedGoogle Scholar
  66. Ruiz-Chica J, Medina MA, Sanchez-Jimenez F, Ramirez FJ (2003) Raman Spectroscopy study of the interaction between biogenic polyamines and an alternating AT oligodeoxyribonucleotide. Biochim Biophys Acta 1628:11–21PubMedGoogle Scholar
  67. Salvi M, Battaglia V, Mancon M, Colombatto S, Cravanzola C, Calheiros R, Marques MP, Grillo MA, Toninello A (2006) Agmatine is transported into liver mitochondria by a specific electrophoretic mechanism. Biochem J 396:337–345CrossRefPubMedGoogle Scholar
  68. Satriano J, Matsufuji S, Murakami Y, Lortie MJ, Schwartz D, Kelly CJ, Hayashi S, Blantz RC (1998) Agmatine suppresses proliferation by frameshift induction of antizyme and attenuation of cellular polyamine levels. J Biol Chem 273:15313–15316CrossRefPubMedGoogle Scholar
  69. Satriano J, Kelly CJ, Blantz RC (1999) An emerging role for agmatine. Kidney Int 56:1252–1253CrossRefPubMedGoogle Scholar
  70. Sava IG, Battaglia V, Rossi CA, Salvi M, Toninello A (2006) Free radical scavenging action of the natural polyamine spermine in rat liver mitochondria. Free Radic Biol Med 41:1272–1281CrossRefPubMedGoogle Scholar
  71. Scalabrino G, Ferioli ME (1981) Polyamines in mammalian tumors. Part I. Adv Cancer Res 35:151–268CrossRefPubMedGoogle Scholar
  72. Scalabrino G, Ferioli ME (1982) Polyamines in mammalian tumors. Part II. Adv Cancer Res 36:1–102CrossRefPubMedGoogle Scholar
  73. Schipper RG, Penning LC, Verhofstad AA (2000) Involvement of polyamines in apoptosis. Facts and controversies: effectors or protectors? Semin Cancer Biol 10:55–68CrossRefPubMedGoogle Scholar
  74. Seiler N, Raul F (2005) Polyamines and apoptosis. J Cell Mol Med 9:623–642CrossRefPubMedGoogle Scholar
  75. Simonian AR, Grigorenko NA, Vepsalainen J, Khomutov AR (2005) New charge-deficient agmatine analogs. Bioorg Khim 31:583–587CrossRefGoogle Scholar
  76. Teixeira LJ, Seabra M, Reis E, Girão da Cruz MT, Pedroso de Lima MC, Pereira E, Miranda MA, Marques MPM (2004) Cytotoxic activity of metal complexes of biogenic polyamines: polynuclear platinum(II). J Med Chem 47:2917–2925CrossRefPubMedGoogle Scholar
  77. Todd BA, Parsegian VA, Shirahata A, Thomas TJ, Rau DC (2008) Attractive forces between cation condensed DNA double helices. Biophys J 94:4775–4782CrossRefPubMedGoogle Scholar
  78. Toninello A, Salvi M, Mondovì B (2004) Interaction of biologically active amines with mitochondria and their role in the mitochondrial-mediated pathway of apoptosis. Curr Med Chem 11:2349–2374PubMedGoogle Scholar
  79. Toninello A, Battaglia V, Salvi M, Calheiros R, Marques MPM (2006) Structural characterisation of agmatine at physiological conditions. Struct Chem 17:163–175CrossRefGoogle Scholar
  80. Vargiu C, Cabella C, Belliardo S, Cravanzola C, Grillo MA, Colombatto S (1999) Agmatine modulates polyamine content in hepatocytes by inducing spermidine/spermine acetyltransferase. Eur J Biochem 259:933–938CrossRefPubMedGoogle Scholar
  81. Von Hoff DD (1994) MGBG: teaching an old drug new tricks. Ann Oncol 5:487–493Google Scholar
  82. Wallace HM (2003) Polyamines and their role in human disease—an introduction. Biochem Soc Trans 31:354–355CrossRefPubMedGoogle Scholar
  83. Wallace HM (2007) Targeting polyamine metabolism: a viable therapeutic/preventative solution for cancer? Expert Opin Pharmacother 8:2109–2116CrossRefPubMedGoogle Scholar
  84. Wallace HM, Fraser AV, Hughes A (2003) A perspective of polyamine metabolism. Biochem J 376:1–14CrossRefPubMedGoogle Scholar
  85. Williams-Ashman HG, Schenone A (1972) Methyl glyoxal bis(guanylhydrazone) as a potent inhibitor of mammalian and yeast S-adenosylmethionine decarboxylases. Biochem Biophys Res Commun 46:288–295CrossRefPubMedGoogle Scholar

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

Personalised recommendations