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

Yukio Katsuki, Yasunori Shibutani, Daisuke Aoki, Shiro Nozawa

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)169-176
Number of pages8
JournalCancer
Volume79
Issue number1
DOIs
Publication statusPublished - 1997 Jan 1

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dienogest
Progestins
Steroids
Hormones
Neoplasms
Progesterone Receptors
MCF-7 Cells
Growth
Norethindrone
Cell Line
Medroxyprogesterone Acetate

Keywords

  • breast carcinoma
  • dienogest
  • endometrial carcinoma
  • mice

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Dienogest, a novel synthetic steroid, overcomes hormone-dependent cancer in a different manner than progestins. / Katsuki, Yukio; Shibutani, Yasunori; Aoki, Daisuke; Nozawa, Shiro.

In: Cancer, Vol. 79, No. 1, 01.01.1997, p. 169-176.

Research output: Contribution to journalArticle

Katsuki, Yukio ; Shibutani, Yasunori ; Aoki, Daisuke ; Nozawa, Shiro. / Dienogest, a novel synthetic steroid, overcomes hormone-dependent cancer in a different manner than progestins. In: Cancer. 1997 ; Vol. 79, No. 1. pp. 169-176.
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AB - 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.

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