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Authors have previously shown that alpha-mercaptopropionylglycine (alpha-MPG) and sodium dipropylacetate (DPA) facilitate immunity as well as host-mediated anti-tumor activity. In this study, we found that a compound related to alpha-MPG and DPA, (2-n-propyl-n-pentanoyl)glycine (KN-539), inhibited the growth of E.L.4 lymphosarcoma transplanted in C57BL/6 mice and further investigated the anti-tumor effects of 1-(4-carboxy-n-neptyl)-5-FU (KN-826) and 1-(4-carboxymethylaminocarbonyl-n-heptyl)-5-FU (KN-827), in which DPA and KN-539 were combined, respectively, to 5-fluorouracil (5-FU). KN-827 showed stronger anti-tumor activity than KN-826, and it was also effective with oral administration. Although KN-827 demonstrated anti-tumor activity two to three times weaker than N1-(2-tetrahydrofuryl)-5-FU (FT-207), KN-827 did not reduce the blood leukocyte count and the number of spleen cells. Furthermore, KN-827 stimulated the production of the hemolytic plaque forming cell (HPFC) in the spleen of mice immunized with sheep-erythrocytes. In contrast, FT-207 and 5-FU obviously reduced not only HPFC-production but also the number of spleen cells.

Anti-tumor effect of new 5-fluorouracil derivatives and their influences on the immune response.