The gastrointestinal polyamine source depletion enhances DFMO induced polyamine depletion in MCF-7 human breast cancer cells in vivo.
Due to the polyamine requirement for cell growth, blockade of polyamine biosynthesis is considered a potential anticancer target. The lack of efficacy of DFMO in vivo, has been attributed to other sources of polyamines, mainly from the gastrointestinal tract (alimentary and bacterial). An experiment was designed to test the role of intestinal polyamine deletion in addition to DFMO (a specific inhibitor of ODC) in established MCF-7 tumors in nude mice. Using DFMO and polyamine-free diet, the tumor putrescine concentrations were more profoundly decreased in comparison to DFMO alone and cellular spermine was also depleted, as has never been observed with DFMO alone. The blockade of the gastrointestinal sources of polyamines enhances the intracellular polyamine depletion induced by DFMO on MCF-7 tumor in nude mice.
Service de Chirurgie, Centre Régional de Lutte Contre le Cancer. Rennes, France.
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J
Levêque
F
F
Burtin
V
V
Catros-Quemener
R
R
Havouis
J P
JP
Moulinoux
D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D002455:Cell Division; D004032:Diet; D000518:Eflornithine / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D011073:Polyamines / Q000008:administration & dosage / Q000378:metabolism*; D013096:Spermine / Q000378:metabolism; D013997:Time Factors; D014183:Transplantation, Heterologous
D011073:Polyamines; D013096:Spermine; D000518:Eflornithine