The anti-melanoma activity of inulin in mice

Abstract

Finely divided, insoluble inulin (gamma polymorph), given intraperitoneally (i.p.) to C57BL mice 1-3 days after i.p. B16 melanoma cells, very significantly increased their mean survival time (MST) in low doses (less than or equal to 40 and less than or equal to 100 micrograms/mouse in 50 and 80% of tests, respectively). The gamma inulin was pure and free of endotoxin and soluble inulin, and was developed as a potent reagent specific for activating the alternative pathway of complement (APC). Its antitumour action paralleled its in vitro APC activation, namely, both activities were sharply dose-dependent up to a threshold dose above which they were dose-independent; dissolved inulin was inactive in vitro and in vivo, decreased the MST of the mice and in a mixture antagonized the in vitro and in vivo activities of gamma inulin; the more soluble (alpha) polymorphs were active in proportion to their gamma content but the effects were blocked at higher doses presumably by dissolved inulin. In addition, depletion of host APC with cobra venom factor or inulin before giving B16 cells increased their malignancy and abrogated the subsequent antitumour action of gamma inulin. The minimum i.p. dose of gamma inulin found to activate serum APC in vivo was 50 micrograms (2.5 mg/kg), i.e. close to the minimum antitumour dose. These close correlations and the specificity of the reagent indicate that activation in vivo of the APC (cellular or humoral) is an important first contact in stimulating host antitumour defences in this mouse model.