title: Inducible expression of maize polyamine oxidase in the nucleus of MCF-7 human breast cancer cells confers sensitivity to etoposide.
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.
authors.affiliation: Department of Biochemical Sciences A. Rossi Fanelli, University of Rome La Sapienza, Rome, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Marcocci
authors.forename: M
authors.initials: M
authors.lastname: Casadei
authors.forename: C
authors.initials: C
authors.lastname: Faso
authors.forename: A
authors.initials: A
authors.lastname: Antoccia
authors.forename: P
authors.initials: P
authors.lastname: Stano
authors.forename: S
authors.initials: S
authors.lastname: Leone
authors.forename: B
authors.initials: B
authors.lastname: Mondovì
authors.forename: R
authors.initials: R
authors.lastname: Federico
authors.forename: P
authors.initials: P
authors.lastname: Tavladoraki
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000235:genetics*; D049109:Cell Proliferation / Q000187:drug effects; D004318:Doxycycline / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology* / Q000627:therapeutic use; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics / Q000378:metabolism*; D011073:Polyamines / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D003313:Zea mays / Q000201:enzymology* / Q000235:genetics; D000097667:Polyamine Oxidase
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004318:Doxycycline; D005047:Etoposide; D000587:Oxidoreductases Acting on CH-NH Group Donors; D011073:Polyamines; D011994:Recombinant Proteins; D000097667:Polyamine Oxidase