Potential Cancer-Chemopreventive Activities of Wine Stilbenoids and Flavans Extracted From Grape (Vitis vinifera) Cell Cultures

• Published in: Nutrition and cancer 2001-01, Vol.40 (2), p.173-179
• Main Authors: Waffo-Téguo, Pierre, Hawthorne, Michael E., Cuendet, Muriel, Mérillon, Jean-Michel, Kinghorn, A. Douglas, Pezzuto, John M., Mehta, Rajendra G.
• Format: Article
• Language: English
• Subjects: 9,10-Dimethyl-1,2-benzanthracene; Animals; Anticarcinogenic Agents - pharmacology; Anticarcinogenic Agents - therapeutic use; Biflavonoids; Biological and medical sciences; Carcinogenesis, carcinogens and anticarcinogens; Catechin - analogs & derivatives; Catechin - pharmacology; Catechin - therapeutic use; Cells, Cultured; Chromatography, High Pressure Liquid; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors - pharmacology; Female; Foods and miscellaneous; Isoenzymes - antagonists & inhibitors; Isoenzymes - metabolism; Mammary Neoplasms, Experimental - chemically induced; Mammary Neoplasms, Experimental - prevention & control; Medical sciences; Membrane Proteins; Mice; Mice, Inbred BALB C; Organ Culture Techniques; Oxygen Consumption; Phenols - isolation & purification; Plant Extracts - chemistry; Proanthocyanidins; Prostaglandin-Endoperoxide Synthases - metabolism; Stilbenes - pharmacology; Stilbenes - therapeutic use; Tumors; Vitis - chemistry; Wine - analysis
• ISSN: 0163-5581; 1532-7914
• DOI: 10.1207/S15327914NC402_14

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 B'2 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 μg/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 (IC 50 50) = 14.9 μM, 96%] vs. cis-resveratrol (IC 50 = 55.4 μM). In the COX-2 assay, among the compounds tested, only trans- and cis-resveratrol exhibited significant inhibitory activity (IC 50 = 32.2 and 50.2 μM, 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.