The gastrointestinal polyamine source depletion enhances DFMO induced polyamine depletion in MCF-7 human breast cancer cells in vivo
Levêque, J.; Burtin, F.; Catros-Quemener, V.; Havouis, R.; Moulinoux, J.P.
Anticancer Research 18(4a): 2663-2668
1998
ISSN/ISBN: 0250-7005 PMID: 9703925 Document Number: 491008
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.