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

Amino Acids. 2008 Apr;34(3):403-12. doi: 10.1007/s00726-007-0558-4. Epub 2007 Jul 4.

Abstract

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 H(2)O(2), 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Nucleus / genetics*
  • Cell Proliferation / drug effects
  • Doxycycline / pharmacology
  • Etoposide / pharmacology*
  • Etoposide / therapeutic use
  • Gene Expression Regulation, Enzymologic* / drug effects
  • Humans
  • Oxidoreductases Acting on CH-NH Group Donors / genetics
  • Oxidoreductases Acting on CH-NH Group Donors / metabolism*
  • Polyamine Oxidase
  • Polyamines / metabolism
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Zea mays / enzymology*
  • Zea mays / genetics

Substances

  • Antineoplastic Agents, Phytogenic
  • Polyamines
  • Recombinant Proteins
  • Etoposide
  • Oxidoreductases Acting on CH-NH Group Donors
  • Doxycycline