Dienogest, a synthetic steroid, suppresses both embryonic and tumor-cell-induced angiogenesis

Nakamura M, Masaki Nakamura, M Nakamura, Katsuki Y, Y Katsuki, Yukio Katsuki, Yasunori Shibutani, Y Shibutani, Shibutani Y, T Oikawa, Tsutomu Oikawa, Oikawa T
European journal of pharmacology · 1999 · vol. 386(1) , pp. 33–40 · doi:10.1016/s0014-2999(99)00765-7 · PMID:10611461 · W1989326112
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Dienogest, a synthetic steroid, was found to suppress both embryonic and tumor-cell-induced angiogenesis.

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Abstract

Orally administered dienogest (17alpha-cyanomethyl-17beta-hydroxy-estra-4,9-diene-3-one) is efficacious against human hormone-dependent cancer xenografts in severely immunodeficient mice and in rats with experimental endometriosis, but its mechanisms of action remain unclear. We assessed the effect of dienogest on angiogenesis, because these two diseases that are sensitive to dienogest are known to be angiogenesis-dependent. Topical dienogest treatment dose-dependently inhibited embryonic angiogenesis, the ID(50) value being 6.4 nmol/egg. Oral administration of dienogest (1 mg kg(-1) day(-1)) for 5 consecutive days significantly suppressed angiogenesis induced by S-180 mouse tumor cells in the mouse dorsal air sac assay. In vitro experiments showed that dienogest at concentrations up to 10 microM had little or no effect on the proliferation of plasminogen activator activity or formation of tube-like structures by microvascular endothelial cells. These results suggest that dienogest is a new, orally active antagonist of angiogenesis, and that its anti-angiogenic action may be involved in its therapeutic effects on cancer xenografts and endometriosis that we observed previously.

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MeSH descriptors

Angiogenesis Inhibitors Antineoplastic Agents, Hormonal Embryo, Mammalian Nandrolone Neovascularization, Pathologic Neovascularization, Physiologic Angiogenesis Inhibitors Animals Antineoplastic Agents, Hormonal Cell Division Cell Division Chorion Chorion Depression, Chemical Embryo, Mammalian Endothelium, Vascular Endothelium, Vascular Endothelium, Vascular Female Mice

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