Potentiation of natural killer cell activity and tumor immunity by diacetylputrescine.

Abstract

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.

• Authors: T L Bowlin, A Rosenberger, D Stemerick, M L Edwards
• Journal: Cancer research (Cancer Res) Vol. 50 Issue 17 Pg. 5460-3 (Sep 01 1990) ISSN: 0008-5472 [Print] United States
• PMID: 2386950 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• diacetylputrescine
• Putrescine

Topics

• Adenocarcinoma (drug therapy)
• Animals
• Antineoplastic Agents (pharmacology)
• Cell Line
• Colonic Neoplasms (drug therapy)
• Cytotoxicity, Immunologic (drug effects)
• Killer Cells, Natural (drug effects, immunology)
• Kinetics
• Liver Neoplasms (drug therapy, secondary)
• Mice
• Mice, Inbred C57BL
• Putrescine (analogs & derivatives, pharmacology, therapeutic use)
• Spleen (immunology)
• Tumor Cells, Cultured (immunology)