THE GASTROINTESTINAL POLYAMINE SOURCE DEPLETION ENHANCES DFMO INDUCEDPOLYAMINE DEPLETION IN MCF-7 HUMAN BREAST-CANCER CELLS IN-VIVO

Due to the polyamine requirement for cell growth, blockade of polyamin e biosynthesis is,considered a potential anticancer target The lack of efficacy of DFMO in vivo, has been attributed to other sources of pol yamines, mainly from the gastrointestinal tract (alimentary and bacter ial). An experiment was designed to test the role of intestinal polyam ine deletion in addition to DFMO (a specific inhibitor of ODC) in esta blished 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 gastroint estinal sources of polyamines enhances the intracellular polyamine dep letion induced by DFMO on MCF-7 tumor in nude mice.