Potential Cancer-Chemopreventive Activities of Wine Stilbenoids and Flavans Extracted From Grape (Vitis vinifera) Cell Cultures
Potential Cancer-Chemopreventive Activities of Wine Stilbenoids and Flavans Extracted From Grape (Vitis vinifera) Cell Cultures
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DOI：
10.1207/s15327914nc402_14
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发表时间：
2001-05
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影响因子：
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通讯作者：
P. Waffo-Téguo;M. Hawthorne;M. Cuendet;J. Mérillon;A. Kinghorn;J. Pezzuto;R. Mehta
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文献类型：
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作者：
P. Waffo-Téguo;M. Hawthorne;M. Cuendet;J. Mérillon;A. Kinghorn;J. Pezzuto;R. Mehta
适量饮用葡萄酒与降低癌症风险有关。利用葡萄植物细胞培养物纯化了12种酚类化合物：芪类化合物trans-astringin、trans-piceid（2）、trans-resveratroloside、trans-resveratrol、trans-piceatannol、cis-resveratroloside、cis-piceid、cis-resveratrol;黄烷（+）-儿茶素、（-）-表儿茶素、表儿茶素3′-O-没食子酸酯;黄烷二聚体矢车菊苷B '2 3′-O-没食子酸酯。评价了这些化合物在器官培养中抑制致癌剂处理的小鼠乳腺中的环氧合酶和癌前病变形成的潜力。在10 μg/ml浓度下，反式-收敛苷和反式-云杉醇抑制小鼠乳腺中7，12-二甲基苯并[a]蒽诱导的癌前病变的发展，与未处理的腺体相比，抑制率分别为68.8%和76.9%。后一种化合物是在该测定中测试的12种化合物中最有效的，除了反式白藜芦醇（87.5%抑制）。在环氧合酶（考克斯）-1测定中，芪类化合物的反式异构体似乎比顺式异构体更有活性：反式白藜芦醇[50%抑制浓度（IC 50 50）= 14.9 μM，96%] vs.顺式白藜芦醇（IC 50 = 55.4 μM）。在考克斯-2试验中，在测试的化合物中，只有反式和顺式白藜芦醇表现出显著的抑制活性（IC 50分别为32.2和50.2 μM）。这是第一个报告显示潜在的癌症化学预防活性的反式收敛剂，一种植物芪类最近发现的葡萄酒。在小鼠乳腺器官培养试验中，反式-Astringin及其苷元反式-Piceatannol具有活性，但在考克斯-1和考克斯-2试验中没有表现出活性。反式白藜芦醇在本研究中使用的所有三种生物测定中均具有活性。这些发现表明，反式收敛苷和反式云杉醇可能作为潜在的癌症化学预防剂的机制不同于反式白藜芦醇。
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 (IC5050) = 14.9 μM, 96%] vs. cis-resveratrol (IC50 = 55.4 μM). In the COX-2 assay, among the compounds tested, only trans- and cis-resveratrol exhibited significant inhibitory activity (IC50 = 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.