The role of the chemical compound RMI 10,874DA (3,6-bis[2-(dimethylamino)-ethoxyl]-9H-
xanthene-9-one dihydrochloride) in the abrogation of the metastatic spread of
tumor cells was studied. Pre-treatment of BALB/c mice with the RMI 10,874DA compound (referred to below as
tilorone analogue) completely eliminated lung colonization of an H-2-negative (GR9.B9) MCA-induced
fibrosarcoma clone in an experimental
metastasis assay. Other murine
tumors, including H-2-positive and H-2-negative chemically induced
fibrosarcoma clones and
B16 melanoma, were also sensitive to the treatment; orally administered
tilorone analogue given one day before the i.v. injection of
tumor cells markedly inhibited lung colonization. The effect was not due to direct toxicity of
tilorone analogue on
tumor cells, but instead it was dependent on NK cells; this was suggested by the finding that anti-asialo GM, treatment of mice abrogated the effect of
tilorone analogue. Kinetic studies of splenic NK activity in
tilorone-treated mice showed a rapid boosting of NK-cell activity, the greatest stimulation occurring the day before removal of splenocytes for 51Cr-release assay against YAC-I target cells. These kinetics correlated with the inhibition of in vivo lung colonization after
tilorone analogue treatment. Inhibition of experimental
tumor metastasis was dose-dependent and was observed when animals were treated the day before or the day after
tumor-cell injection. Furthermore, repeated treatment of mice with this
tilorone analogue significantly reduced lung colonization.