Natural Inhibitors of Carcinogenesis

A. Douglas Kinghorn; Bao-Ning Su; Dae Sik Jang; Leng Chee Chang; Dongho Lee; Jian-Qiao Gu; Esperanza J. Carcache-Blanco; Alison D. Pawlus; Sang Kook Lee; Eun Jung Park; Muriel Cuendet; Joell J. Gills; Krishna Bhat; Hye-Sung Park; Eugenia Mata-Greenwood; Lynda L. Song; Meishiang Jang; John M. Pezzuto

doi:10.1055/s-2004-827198

Planta Med 2004; 70(8): 691-705
DOI: 10.1055/s-2004-827198

Review

Natural Inhibitors of Carcinogenesis

A. Douglas Kinghorn¹ , Bao-Ning Su¹ , Dae Sik Jang¹ ^, ³ , Leng Chee Chang¹ ^, ⁴ , Dongho Lee¹ ^, ⁵ , Jian-Qiao Gu¹ ^, ⁶ , Esperanza J. Carcache-Blanco¹ , Alison D. Pawlus¹ , Sang Kook Lee¹ ^, ² , Eun Jung Park¹ ^, ⁷ , Muriel Cuendet¹ , Joell J. Gills¹ , Krishna Bhat¹ ^, ⁹ , Hye-Sung Park¹ , Eugenia Mata-Greenwood¹ ^, ¹⁰ , Lynda L. Song¹ ^, ¹¹ , Meishiang Jang¹ ^, ¹² , John M. Pezzuto¹ ^, ²

¹Program for Collaborative Research in the Pharmaceutical Sciences, Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA
²Heine Pharmacy Building, Purdue University, West Lafayette, IN, USA
³College of Pharmacy, Ewha Woman’s University, Seoul, Korea
⁴Department of Chemistry, University of Minnesota at Duluth, Duluth, MN, USA
⁵Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea
⁶College of Pharmacy, University of Arizona, Tucson, AZ, USA
⁷DTP-Tumor Hypoxia Laboratory, NCI-Frederick, Frederick, MD, USA
⁸Cancer Therapeutics Branch, NCI, Bethesda, MD, USA
⁹Department of Molecular and Cellular Oncology, University of Texas, M.D. Anderson Cancer Center, Houston, TX, USA
¹⁰Northwestern University, Pediatric Research, Chicago, IL, USA
¹¹Department of Biopharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA
¹²Department of Pathology, Loyola University Chicago, Maywood, IL, USA

Abstract

Previous collaborative work by our group has led to the discovery of several plant isolates and derivatives with activities in in vivo models of cancer chemoprevention, including deguelin, resveratrol, bruceantin, brassinin, 4′-bromoflavone, and oxomate. Using a panel of in vitro bioassays to monitor chromatographic fractionation, a diverse group of plant secondary metabolites has been identified as potential cancer chemopreventive agents from mainly edible plants. Nearly 50 new compounds have been isolated as bioactive principles in one or more in vitro bioassays in work performed over the last five years. Included among these new active compounds are alkaloids, flavonoids, stilbenoids, and withanolides, as well as a novel stilbenolignan and the first representatives of the norwithanolides, which have a 27-carbon atom skeleton. In addition, over 100 active compounds of previously known structure have been obtained. Based on this large pool of potential cancer chemopreventive compounds, structure-activity relationships are discussed in terms of the quinone reductase induction ability of flavonoids and withanolides and the cyclooxygenase-1 and -2 inhibitory activities of flavanones, flavones and stilbenoids. Several of the bioactive compounds were found to be active when evaluated in a mouse mammary organ culture assay, when used as a secondary discriminator in our work. The compounds (2S)-abyssinone II, (2S)-2′,4′-dihydroxy-2″-(1-hydroxy-1-methylethyl)dihydrofuro[2,3-h]-flavanone, 3′-[γ-hydroxymethyl-(E)-γ-methylallyl]-2,4,2′,4′-tetrahydroxychalcone 11′-O-coumarate, isolicoflavonol, isoliquiritigenin, and ixocarpalactone A are regarded as promising leads as potential cancer chemopreventive agents.

Key words

Edible plants - in vitro bioassays - mouse mammary organ culture - potential cancer chemopreventive agents - plant secondary metabolites - flavonoids - stilbenoids - withanolides - structure-activity relationships

Full Text

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A. Douglas Kinghorn

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