title: Potential cancer-chemopreventive activities of wine stilbenoids and flavans extracted from grape (Vitis vinifera) cell cultures.
abstract: Moderate consumption of wine is associated with a reduced risk of cancer. Grape plant cell cultures were used to purify 12 phenols: the stilbenoids trans-astringin, trans-piceid (2), trans-resveratroloside, trans-resveratrol, trans-piceatannol, cis-resveratroloside, cis-piceid, and cis-resveratrol; the flavans (+)-catechin, (-)-epicatechin, and epicatechin 3-O-gallate; and the flavan dimer procyanidin B2 3'-O-gallate. These compounds were evaluated for potential to inhibit cyclooxygenases and preneoplastic lesion formation in carcinogen-treated mouse mammary glands in organ culture. At 10 micrograms/ml, trans-astringin and trans-piceatannol inhibited development of 7,12-dimethylbenz[a]anthracene-induced preneoplastic lesions in mouse mammary glands with 68.8% and 76.9% inhibition, respectively, compared with untreated glands. The latter compound was the most potent of the 12 compounds tested in this assay, with the exception of trans-resveratrol (87.5% inhibition). In the cyclooxygenase (COX)-1 assay, trans isomers of the stilbenoids appear to be more active than cis isomers: trans-resveratrol [50% inhibitory concentration (IC50) = 14.9 microM, 96%] vs. cis-resveratrol (IC50 = 55.4 microM). In the COX-2 assay, among the compounds tested, only trans- and cis-resveratrol exhibited significant inhibitory activity (IC50 = 32.2 and 50.2 microM, respectively). This is the first report showing the potential cancer-chemopreventive activity of trans-astringin, a plant stilbenoid recently found in wine. trans-Astringin and its aglycone trans-piceatannol were active in the mouse mammary gland organ culture assay but did not exhibit activity in COX-1 and COX-2 assays. trans-Resveratrol was active in all three of the bioassays used in this investigation. These findings suggest that trans-astringin and trans-piceatannol may function as potential cancer-chemopreventive agents by a mechanism different from that of trans-resveratrol.
authors.affiliation: Program for Collaborative Research in the Pharmaceutical Sciences, Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: P
authors.initials: P
authors.lastname: Waffo-Téguo
authors.forename: M E
authors.initials: ME
authors.lastname: Hawthorne
authors.forename: M
authors.initials: M
authors.lastname: Cuendet
authors.forename: J M
authors.initials: JM
authors.lastname: Mérillon
authors.forename: A D
authors.initials: AD
authors.lastname: Kinghorn
authors.forename: J M
authors.initials: JM
authors.lastname: Pezzuto
authors.forename: R G
authors.initials: RG
authors.lastname: Mehta
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D044946:Biflavonoids; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000627:therapeutic use; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D005260:Female; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000517:prevention & control; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D009924:Organ Culture Techniques; D010101:Oxygen Consumption; D010636:Phenols / Q000302:isolation & purification; D010936:Plant Extracts / Q000737:chemistry*; D044945:Proanthocyanidins; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology* / Q000627:therapeutic use; D027843:Vitis / Q000737:chemistry*; D014920:Wine / Q000032:analysis*
chemical_list: D016588:Anticarcinogenic Agents; D044946:Biflavonoids; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D010636:Phenols; D010936:Plant Extracts; D044945:Proanthocyanidins; D013267:Stilbenes; C479580:procyanidin B2; D015127:9,10-Dimethyl-1,2-benzanthracene; D002392:Catechin; C062669:epicatechin gallate; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496512:Ptgs1 protein, mouse; D000077185:Resveratrol