Inhibitory effect of munetone, an isoflavonoid, on 12-O-tetradecanoylphorbol 13-acetate-induced ornithine decarboxylase activity

Starting with an extract: derived from the bark of Mundulea sericea Willd, (Leguminosae) that was active in the process of inhibiting 12-O-tetradecano ylphorbol 13-acetate (TPA)-induced ornithine decarboxylase activity (ODC) i n cultured mouse epidermal ME 308 cells, the isoflavonoid munetone was isol ated and identified as an active principle (IC50 = 46 ng/ml). Topical appli cation of munetone (0.04-5 mu mol) to the skin of CD-1 mice 2 h prior to tr eatment with TPA (10 nmol) resulted in dose-dependent inhibition of epiderm al ODC activity. In addition, munetone inhibited TPA-independent c-Myc-indu ced ODC activity with cultured BALB/c c-MycER cells, as well as 7,12-dimeth ylbenz[a]anthracene (DMBA)-induced preneoplastic lesion formation in a mous e mammary gland organ culture (MMOC) system. These data suggest the potenti al of munetone to serve as a cancer chemopreventive agent by virtue of bloc king the process of tumor promotion. (C) 1999 Published by Elsevier Science Ltd. All rights reserved.