Potentiation of natural killer cell activity and tumor immunity by diacetylputrescine.
The objective of the present investigation was to evaluate the immunomodulating properties of tetramethylenebisacetamide (N,N' 1-diacetylputrescine, DAP), a known inducer of cellular differentiation. We examined the effect of DAP administration in vivo on splenic and nonadherent peritoneal natural killer (NK) cell activity. A single i.p. injection of DAP (100 mg/kg) enhanced cytolytic activity directed against YAC-1 and MCA-38 tumor target cells 2- to 3-fold. Cytolytic activity peaked 3 days following DAP injection. DAP treatment increased the frequency of asialo-GM1-positive splenocytes to 15% compared with 5% for vehicle treated controls. Furthermore, cytolytic activity could be eliminated by treatment with anti-asialo-GM1 antibodies and complement. Lysis of NK-resistant P815 and EL4 tumor target cells was not observed in leukocytes from DAP-treated mice. DAP treatment of mice given injections i.p. of MCA-38 tumor cells increased survival time of the mice by 37%, curing 10% of the animals of the tumor. DAP treatment of mice given injections intrasplenically of MCA-38 tumor cells reduced both the number and the size of the hepatic metastases. The antitumor effect of DAP in vivo could be eliminated by pretreating mice with anti-asialo-GM1 antibodies or utilizing NK cell deficient beige (bg/bg) mice. These results indicate that the observed anti-tumor activity of DAP is mediated, at least in part, by NK cells.
Bowlin
T L
TL
Merrell Dow Research Institute, Cincinnati, Ohio 45215.
Rosenberger
A
A
Stemerick
D
D
Edwards
M L
ML
D000230:Adenocarcinoma / Q000188:drug therapy*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002460:Cell Line; D003110:Colonic Neoplasms / Q000188:drug therapy*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D007700:Kinetics; D008113:Liver Neoplasms / Q000188:drug therapy / Q000556:secondary*; D051379:Mice; D008810:Mice, Inbred C57BL; D011700:Putrescine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D013154:Spleen / Q000276:immunology; D014407:Tumor Cells, Cultured / Q000276:immunology
D000970:Antineoplastic Agents; C063620:diacetylputrescine; D011700:Putrescine