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.