Anti-tumor-Promoting activity of tibolone and its metabolites.

Abstract

The aim of this study was to evaluate the cancer chemopreventive potential of the widely prescribed drug tibolone (17alpha-ethynyl-7alpha-methyl-5(10)-estren-3-one, CAS 5630-53-5) and its main metabolites, 17alpha-ethynyl-7alpha-methyl-4-estren-3-one (CAS 1162-60-3), 17alpha-ethynyl-7alpha-methyl-5(10)-estrene-3alpha,17beta-diol (CAS 100239-44-9) and 17alpha-ethynyl-7alpha-methyl-5(10)-estrene-3beta,17beta-diol (CAS 100239-45-0), by studying their anti-tumor-promoting activity. To this aim the test compounds were submitted to the short term in vitro assay for the inhibition of Epstein-Barr virus early antigen (EBV-EA) activation induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) as a primary screening for anti-tumor promoters. All the compounds showed high inhibitory activity and low cytotoxicity as compared to literature data. To extend the study to an animal model, tibolone and its 3alpha-hydroxy metabolite (CAS 100239-44-9) were also assayed in the in vivo two-stage on mouse skin carcinogenesis test, exhibiting significant inhibitory effects on TPA promoted mouse skin papillomas formation. A comparison with literature data indicated them as more potent compounds than other steroids previously studied such as digitoxigenin, cortisone, hydrocortisone, and prednisolone.

• Authors: Diego Colombo, Patrizia Ferraboschi, Laura Franchini, Hoyoku Nishino, Jyunko Takayasu, Harukuni Tokuda
• Journal: Arzneimittel-Forschung (Arzneimittelforschung) Vol. 58 Issue 2 Pg. 86-90 ( 2008) ISSN: 0004-4172 [Print] Germany
• PMID: 18412022 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anticarcinogenic Agents
• Carcinogens
• Epstein-Barr Virus Nuclear Antigens
• Norpregnenes
• Selective Estrogen Receptor Modulators
• tibolone
• Tetradecanoylphorbol Acetate

Topics

• Animals
• Anticarcinogenic Agents
• Carcinogens (antagonists & inhibitors, toxicity)
• Cell Line, Tumor
• Epstein-Barr Virus Nuclear Antigens (drug effects)
• Female
• Mice
• Norpregnenes (pharmacokinetics, pharmacology)
• Papilloma (chemically induced, prevention & control)
• Selective Estrogen Receptor Modulators (pharmacokinetics, pharmacology)
• Skin Neoplasms (chemically induced, prevention & control)
• Tetradecanoylphorbol Acetate (antagonists & inhibitors, toxicity)