Amino Acids

, Volume 34, Issue 3, pp 403–412 | Cite as

Inducible expression of maize polyamine oxidase in the nucleus of MCF-7 human breast cancer cells confers sensitivity to etoposide

  • L. Marcocci
  • M. Casadei
  • C. Faso
  • A. Antoccia
  • P. Stano
  • S. Leone
  • B. Mondovì
  • R. Federico
  • P. Tavladoraki
Article

Summary.

In this study, polyamine oxidase from maize (MPAO), which is involved in the terminal catabolism of spermidine and spermine to produce an aminoaldehyde, 1,3-diaminopropane and H2O2, has been conditionally expressed at high levels in the nucleus of MCF-7 human breast cancer cells, with the aim to interfere with polyamine homeostasis and cell proliferation. Recombinant MPAO expression induced accumulation of a high amount of 1,3-diaminopropane, an increase of putrescine levels and no alteration in the cellular content of spermine and spermidine. Furthermore, recombinant MPAO expression did not interfere with cell growth of MCF-7 cells under normal conditions but it did confer higher growth sensitivity to etoposide, a DNA topoisomerase II inhibitor widely used as antineoplastic drug. These data suggest polyamine oxidases as a potential tool to improve the efficiency of antiproliferative agents despite the difficulty to interfere with cellular homeostasis of spermine and spermidine.

Keywords: Polyamines – Polyamine oxidase – Hydrogen peroxide – Aminoaldehydes – Etoposide – Human breast cancer cells – Terminal catabolism 

Abbreviations:

BSA

Bovine serum albumin

CuAO

copper-dependent amine oxidases

Dah

1,6-diaminohexane

Dap

1,3-diaminopropane

DAPI

4′,6′-diamidino-2-phenylindole dihydrochloride

DMEM

Dulbecco’s modified Eagle’s medium

Dox

doxycycline

etoposide

4′-demethylepipodophyllotoxin 9-(4,6-O-ethylidene-β-d-glucopyranoside)

FITC

fluoroscein-isothiocyanate

MDL72527

N1,N4-bis(2,3-butadienyl)-1,4-butanediamine

MPAO

maize polyamine oxidase

NLS

nuclear localization signal

PAO

polyamine oxidases

PMSF

phenylmethylsulfonylfluoride

Put

putrescine

ROS

reactive oxygen species

SMO

spermine oxidases

Spd

spermidine

Spm

spermine

SSAT

spermine/spermidine acetyl transferase

Tet

tetracycline

XTT

sodium 3′-(1-(phenylamino-carbonyl)-3,4-tetrazolium)-bis (4-methoxy-6-nitro) benzene sulfonic acid

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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • L. Marcocci
    • 1
  • M. Casadei
    • 2
  • C. Faso
    • 2
  • A. Antoccia
    • 2
  • P. Stano
    • 2
  • S. Leone
    • 2
  • B. Mondovì
    • 1
  • R. Federico
    • 2
  • P. Tavladoraki
    • 2
  1. 1.Department of Biochemical Sciences ‘A. Rossi Fanelli’University of Rome ‘La Sapienza’RomeItaly
  2. 2.Department of BiologyUniversity ‘Roma Tre’RomeItaly

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