POSITIVE INTERACTIONS BETWEEN HUMAN INTERFERON AND CEPHARANTHIN AGAINST HUMAN CANCER-CELLS IN-VITRO AND IN-VIVO

A human tumor microcytotoxicity-viable cell-staining assay was used to test the antiproliferative effect of recombinant human interferon-bet a or -gamma alone and in combination with bisbenzylisoquinoline alkalo id cepharanthin against four human tumor cell lines in vitro and in nu de mice. Results obtained in the in vitro study indicate that combinat ions of interferon-beta/-gamma with cepharanthin show synergistic and, occasionally, additive antiproliferative effects in a dose-dependent manner on tumor viable cell-staining assay. Interferon-gamma combined with cepharanthin suppressed the growth of all four human tumor cell l ines (RPMI 4788, PC 10, HeLa, ZR-75-1), and this enhanced antiprolifer ative effect was not dependent on the interferon species involved, inc luding interferon-beta and -gamma. In an experimental model of pulmona ry metastasis, in which human colon tumor cells were inoculated i.v. i nto nude mice, interferon-gamma alone exerted significant inhibitory a ctivity against pulmonary metastasis in a dose-dependent manner, and c epharanthin alone also significantly inhibited metastasis. Furthermore , a combination of interferon-gamma with cepharanthin resulted in a co nsiderable suppression of pulmonary metastasis. These studies indicate that due to their therapeutic potential, combinations of recombinant human interferon-beta or -gamma with cepharanthin might be a promising therapy for pulmonary metastasis of human cancers.