Inducible expression of maize polyamine oxidase in the nucleus of MCF-7 human breast cancer cells confers sensitivity to etoposide.
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.
Marcocci
L
L
Department of Biochemical Sciences A. Rossi Fanelli, University of Rome La Sapienza, Rome, Italy.
Casadei
M
M
Faso
C
C
Antoccia
A
A
Stano
P
P
Leone
S
S
Mondovì
B
B
Federico
R
R
Tavladoraki
P
P
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
D000972:Antineoplastic Agents, Phytogenic; D004318:Doxycycline; D005047:Etoposide; D000587:Oxidoreductases Acting on CH-NH Group Donors; D011073:Polyamines; D011994:Recombinant Proteins; D000097667:Polyamine Oxidase