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-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.
Lee
S K
SK
Program for Collaborative Research in the Pharmaceutical Sciences, College of Pharmacy, Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 60612, USA.
Luyengi
L
L
Gerhäuser
C
C
Mar
W
W
Lee
K
K
Mehta
R G
RG
Kinghorn
A D
AD
Pezzuto
J M
JM
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002273:Carcinogens / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects* / Q000201:enzymology; D007529:Isoflavones / Q000494:pharmacology*; D008321:Mammary Glands, Animal / Q000187:drug effects*; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D009924:Organ Culture Techniques; D065108:Ornithine Decarboxylase Inhibitors; D010936:Plant Extracts / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000378:metabolism*
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D004791:Enzyme Inhibitors; D007529:Isoflavones; D065108:Ornithine Decarboxylase Inhibitors; D010936:Plant Extracts; C118529:munetone; D015127:9,10-Dimethyl-1,2-benzanthracene; D013755:Tetradecanoylphorbol Acetate