Dienogest, a novel synthetic steroid, overcomes hormone-dependent cancer in a different manner than progestins

BACKGROUND. Dienogest is a synthetic progestational steroid that is used for contraception. It is being studied for the treatment of endometriosis, but its anticancer activity remains unknown. The authors investigated the anticancer effect of dienogest on hormone-dependent cancers. METHODS. The authors used two cell lines derived from human endometrial carcinoma (HEC- 88nu cells expressing estrogen receptors [ERI] but not progesterone receptors [PR] and Ishikawa cells expressing both ER and PR) and a cell line derived from human breast carcinoma (MCF-7 cells expressing both ER and PR). The authors examined the in vivo antitumor activity and the antiuterotropic activity of dienogest in mice and compared it with the activity of several progestins. RESULTS. At oral doses of 0.01-1 mg/kg/day, dienogest significantly suppressed tire 17 β estradiol benzoate (E₂) -dependent tumor growth of HEC-88nu cells, which were unresponsive to known progestins such as medroxyprogesterone acetate (MPA, 100 mg/kg/day, administered orally) and norethisterone (NES, 100 mg/kg/day, administered orally). The suppressive effect of dienogest on tumor growth was not diminished in the presence of excess MPA. Dienogest also suppressed the E₂ dependent tumor growth of both Ishikawa and MCF-7 cells, both of which responded to MPA. However, the minimum effective dose of dienogest (0.01-1 mg/kg/day) was much lower than that of MPA (100 mg/kg/day). In contrast, dienogest did not suppress the E₂- induced increase in uterine weight, whereas MPA and NES suppressed it significantly. CONCLUSIONS. Dienogest showed potent anticancer activity against hormone-dependent cancers at doses at which progestins show no activity.