Anti-tumor effect of new 5-fluorouracil derivatives and their influences on the immune response.
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.
D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D005472:Fluorouracil / Q000494:pharmacology*; D007109:Immunity / Q000187:drug effects*; D007274:Injections, Intraperitoneal; D007958:Leukocyte Count; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000188:drug therapy; D013154:Spleen / Q000187:drug effects
D000970:Antineoplastic Agents; D005472:Fluorouracil