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 (17α-ethynyl-7α-methyl-5(10)-estren-3-one, CAS 5630-53-5) and its main metabolites, 17α-ethynyl-7α-methyl-4-estren-3-one (CAS 1162-60-3), 17α-ethynyl-7α-methyl-5(10)-estrene-3α,17β-diol (CAS 100239-44-9) and 17α-ethynyl-7α-methyl-5(10)-estrene-3β,17β-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 3α-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.

Key words

Anti-tumor-promoting compounds - CAS 5630-53-5 - Epstein-Barr virus - Progestins - Steroids - Tibolone, cancer chemoprevention, metabolites

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