Plant phenolics decrease intestinal tumors in an animal model of familial adenomatous polyposis
Plant phenolics decrease intestinal tumors in an animal model of familial adenomatous polyposis
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DOI：
10.1093/carcin/21.5.921
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发表时间：
2000-05-01
期刊：
影响因子：
4.7
通讯作者：
Bertagnolli, MM
中科院分区：
文献类型：
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作者：
Mahmoud, NN;Carothers, AM;Bertagnolli, MM
流行病学研究一直表明，水果和蔬菜的消费降低了人类的癌症风险，并表明某些饮食成分可能在预防结肠癌方面有效。植物来源的酚类化合物表现出许多有益的作用，并可能在体内抑制几个阶段的癌症发生。在这项研究中，我们研究了几种植物来源的酚类化合物，包括咖啡酸苯乙酯(CAPE)、姜黄素、栎素和芦丁，对C57BL/6J-Min/+(Min/+)小鼠的肿瘤预防作用。这些动物携带APC基因的胚系突变，并在15周大时自发发展为许多肠腺瘤。在0.15%的饮食水平下，CAFE将Min/+小鼠的肿瘤形成减少了63%。姜黄素对肿瘤也有类似的抑制作用。然而，在饮食水平为2%的情况下，槲皮素和芦丁都未能改变肿瘤的形成。对处理动物的肠道组织的检查表明，CAFE和姜黄素预防肿瘤与增加肠细胞的凋亡和增殖有关。CAFE和姜黄素还减少了Min/+小鼠肠道细胞中癌蛋白β-连环素的表达，这一观察结果以前与抗肿瘤作用有关，这些数据使植物酚类化合物CAFE和姜黄素成为越来越多抑制Ape相关肠道癌变的抗炎剂之一。
Epidemiological studies consistently indicate that consumption of fruits and vegetables lowers cancer risk in humans and suggest that certain dietary constituents may be effective in preventing colon cancer. Plant-derived phenolic compounds manifest many beneficial effects and can potentially inhibit several stages of carcinogenesis in vivo. In this study, we investigated the efficacy of several plant-derived phenolics, including caffeic acid phenethyl ester (CAPE), curcumin, quercetin and rutin, for the prevention of tumors in C57BL/6J-Min/+ (Min/+) mice. These animals bear a germline mutation in the Apc gene and spontaneously develop numerous intestinal adenomas by 15 weeks of age. At a dietary level of 0.15%, CAFE decreased tumor formation in Min/+ mice by 63%. Curcumin induced a similar tumor inhibition. Quercetin and rutin, however, both failed to alter tumor formation at dietary levels of 2%. Examination of intestinal tissue from the treated animals showed that tumor prevention by CAFE and curcumin was associated with increased enterocyte apoptosis and proliferation. CAFE and curcumin also decreased expression of the oncoprotein beta-catenin in the enterocytes of the Min/+ mouse, an observation previously associated with an antitumor effect, These data place the plant phenolics CAFE and curcumin among a growing list of anti-inflammatory agents that suppress Ape-associated intestinal carcinogenesis.