Planta Med 2004; 70(8): 691-705
DOI: 10.1055/s-2004-827198
Review
© Georg Thieme Verlag KG Stuttgart · New York

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
Further Information

Publication History

Received: January 14, 2004

Accepted: May 8, 2004

Publication Date:
24 August 2004 (online)

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.

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A. Douglas Kinghorn

Present address: College of Pharmacy

The Ohio State University

500 W. 12th Avenue

Columbus, OH 43210-1291-USA

Phone: +1-614-247-8094

Fax: +1-614-247-8081

Email: kinghorn.4@osu.edu

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