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-beta or -gamma alone and in combination with bisbenzylisoquinoline alkaloid cepharanthin against four human tumor cell lines in vitro and in nude mice. Results obtained in the in vitro study indicate that combinations 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 lines (RPMI 4788, PC 10, HeLa, ZR-75-1), and this enhanced antiproliferative effect was not dependent on the interferon species involved, including interferon-beta and -gamma. In an experimental model of pulmonary metastasis, in which human colon tumor cells were inoculated i.v. into nude mice, interferon-gamma alone exerted significant inhibitory activity against pulmonary metastasis in a dose-dependent manner, and cepharanthin alone also significantly inhibited metastasis. Furthermore, a combination of interferon-gamma with cepharanthin resulted in a considerable 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.