FLAT REVERTANT INDUCERS, STYRYL DIPHENYLAMINE DERIVATIVES, INHIBIT GROWTH AND METASTASIS OF MURINE TUMOR-CELLS IN-VIVO

Previously, we reported that a novel styryl diphenylamine derivative, RX-465, reverts the transformed phenotype of human fibrosarcoma HT1080 cells in vitro. To determine whether agents inducing such phenotypic reversion show antitumor and/or antimetastatic effects in vivo, we ass essed tumor growth and metastasis in mice inoculated with either murin e B16-, B16BL6 melanoma or M5076 reticulosarcoma. These mice received orally our new derivatives of RX-465, namely RX-512 and RX-549. We fou nd that these derivatives inhibited B16 melanoma and M5076 reticulosar coma growth by greater than 80% in vivo. RX-512 also inhibited the met astatic dissemination of B16BL6 melanoma into the lung and that of M50 76 reticulosarcoma into the liver by 98% and 100% at doses of 60 and 4 0 mg/kg/day, respectively. These treatments did not cause significant decreases in body weight. Our data strongly demonstrate that styryl di phenylamine derivatives that revert transformed phenotype in vitro pot entially inhibit tumor growth and metastasis in mice with negligible t oxicity at effective doses.