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

Abstract

Starting with an extract derived from the bark of Mundulea sericea Willd. (Leguminosae) that was active in the process of inhibiting 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced ornithine decarboxylase activity (ODC) in cultured mouse epidermal ME 308 cells, the isoflavonoid munetone was isolated and identified as an active principle (IC50 = 46 ng/ml). Topical application of munetone (0.04-5 micromol) to the skin of CD-1 mice 2 h prior to treatment with TPA (10 nmol) resulted in dose-dependent inhibition of epidermal ODC activity. In addition, munetone inhibited TPA-independent c-Myc-induced ODC activity with cultured BALB/c c-MycER cells, as well as 7,12-dimethylbenz[a]anthracene (DMBA)-induced preneoplastic lesion formation in a mouse mammary gland organ culture (MMOC) system. These data suggest the potential of munetone to serve as a cancer chemopreventive agent by virtue of blocking the process of tumor promotion.

• Authors: S K Lee, L Luyengi, C Gerhäuser, W Mar, K Lee, R G Mehta, A D Kinghorn, J M Pezzuto
• Journal: Cancer letters (Cancer Lett) Vol. 136 Issue 1 Pg. 59-65 (Feb 08 1999) ISSN: 0304-3835 [Print] Ireland
• PMID: 10211940 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Anticarcinogenic Agents
• Carcinogens
• Enzyme Inhibitors
• Isoflavones
• Ornithine Decarboxylase Inhibitors
• Plant Extracts
• munetone
• 9,10-Dimethyl-1,2-benzanthracene
• Tetradecanoylphorbol Acetate

Topics

• 9,10-Dimethyl-1,2-benzanthracene
• Animals
• Anticarcinogenic Agents (pharmacology)
• Carcinogens (metabolism)
• Cells, Cultured
• Dose-Response Relationship, Drug
• Enzyme Induction (drug effects)
• Enzyme Inhibitors (pharmacology)
• Epidermal Cells
• Epidermis (drug effects, enzymology)
• Isoflavones (pharmacology)
• Mammary Glands, Animal (drug effects)
• Mammary Neoplasms, Experimental (chemically induced, prevention & control)
• Mice
• Mice, Inbred BALB C
• Organ Culture Techniques
• Ornithine Decarboxylase Inhibitors
• Plant Extracts (pharmacology)
• Tetradecanoylphorbol Acetate (metabolism)