Inhibitory effect of munetone, an iso¯avonoid, on 12-O- tetradecanoylphorbol 13-acetate-induced ornithine decarboxylase activity Sang Kook Lee a, b , Lumonadio Luyengi a, b , Clarissa Gerha Èuser c , Woongchon Mar d , Konjoo Lee a, b , Rajendra G. Mehta e , A. Douglas Kinghorn a, b , John M. Pezzuto a, b, e, * a Program for Collaborative Research in the Pharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, USA b Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, USA c Deutsches Krebsforschungszentrum, Abteilung 0325, Toxikologie und Krebsrisikofaktoren, Im Neuenheimer Feld 280, D-69120, Heidelberg, Germany d Natural Products Research Institute, Seoul National University, Seoul 110-460, South Korea e Department of Surgical Oncology, College of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA Received 11 August 1998; received in revised form 15 September 1998; accepted 18 September 1998 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 iso¯avonoid munetone was isolated and identi®ed as an active principle (IC 50  46 ng/ml). Topical application of munetone (0.04±5 mmol) 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. q 1999 Published by Elsevier Science Ltd. All rights reserved. Keywords: Munetone; 12-O-Tetradecanoylphorbol 13-acetate; Ornithine decarboxylase; c-MycER; Mammary organ culture; Cancer chemo- prevention 1. Introduction The leguminous shrub Mundulea sericea Willd. (syn. M. suberosa) (Leguminosae) is a plant that grows in tropical Africa and parts of India [1]. The bark, leaves and roots of this plant have been used for diverse purposes [2,3]. The isolation of several compounds from this plant has been reported earlier [4±6]. In our search for naturally occurring cancer chemopreventive agents, we have reported the isola- tion of various active compounds, including the rote- noids deguelin and tephrosin, from an ethyl acetate- soluble extract of the bark [7]. These agents were Cancer Letters 136 (1999) 59±65 0304-3835/99/$ - see front matter q 1999 Published by Elsevier Science Ltd. All rights reserved. PII: S0304-3835(98)00309-7 * Corresponding author. Program for Collaborative Research in the Pharmaceutical Sciences (M/C 877), College of Pharmacy, University of Illinois at Chicago, 833 South Wood Street, Chicago, IL 60612, USA. Tel.: 1 1-312-996-5967; fax: 1 1-312-996-2815; e-mail: jpezzuto@uic.edu.