Immunological and antitumor effects of coumarin and some derivatives.
Coumarin and its 4-OH and 7-OH derivatives, as well as o-, m- and p-coumaric acid were tested against P-815 and P-388 tumor cells in vitro. In addition, the compounds were investigated in various in vitro immunological test systems and genuine coumarin was tested furthermore against the Sarcoma-180 in CD1 mice. In vivo, coumarin showed only a moderate antitumor effect against the allogeneic Sarcoma-180 at concentrations of 10 and 40 mg/kg, with inhibition rates of 49 and 60%, respectively. However, both concentrations were markedly toxic. In vitro all compounds were more or less cytotoxic against P-815 and P-388 tumor cell lines starting at a concentration of 100 micrograms/ml. At subtoxic concentrations (less than or equal to 10 micrograms/ml) the samples showed no mitogenic activity against murine spleen lymphocytes and PHA costimulated human peripheral blood lymphocytes. Furthermore, with the coumarin derivatives neither cytotoxic macrophages could be induced against P-815 tumor cells nor an increased release of Il-2 and TNF-alpha could be observed. Only 7-OH coumarin, in concentrations of 2 and 20 micrograms/ml, caused a strong increase in phagocytosis of 124 and 84% in both, human peripheral blood granulocytes and murine peritoneal macrophages, respectively.
Rosskopf
F
F
University of Regensburg, Department of Pharmacy.
Kraus
J
J
Franz
G
G
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003374:Coumarins / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D008214:Lymphocytes / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D010587:Phagocytosis / Q000187:drug effects; D010835:Phytohemagglutinins; D012510:Sarcoma 180 / Q000188:drug therapy; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D003374:Coumarins; D007166:Immunosuppressive Agents; D010835:Phytohemagglutinins