EFFECT OF PLANT PHENOLIC COMPOUNDS ON HUMAN COLON EPITHELIAL CELLS

植物酚类化合物对人结肠上皮细胞的影响

• 批准号: 6115894
• 负责人: STEVEN J SHIFF
• 金额: $ 4.54万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6115894
• 关键词: catechols; chemoprevention; clinical research; colon; colon neoplasms; drug screening /evaluation; eicosanoid metabolism; flavonoids; gastrointestinal epithelium; human subject; nonsteroidal antiinflammatory agent; phenols; plant extracts; quercetin

Colorectal cancer is a common and often fatal cancer. Primary prevention of this important public health problem is feasible because it is substantially influenced by nutritional and pharmacological factors such as dietary fat, fiber, micronutrients (i.e. calcium and selenium, aspirin (ASA), and other nonsteroidal antiinflammatory drugs. Sulindac is a potent chemopreventive agent for colorectal cancer. Quercetin, a plant-derived compound with anti-inflammatory properties, inhibits colon cancer development in preclinical studies. However, its effectiveness in the prevention of human colorectal cancer is unknown. NSAIDs modulate the turnover (induce cell quiescence and apoptosis) of colonic epithelial cells. This effect may be important for their efficacy as colon cancer chemopreventive agents. The goal of this study is to determine the effects sulindac and quercetin on the turnover of human colonic epithelial cells. By comparing and contrasting the effect of these 2 compounds on colonocytes of humans, we hope to begin to understand the effects of NSAID compounds on the physiology of the colorectal crypts of humans. Through these and future studies we eventually hope to predict the potential utility of quercetin as a colon cancer chemopreventive agent and to shed additional light on the mechanisms by which anti-inflammatory agents prevent colon carcinogenesis.

结直肠癌是一种常见且经常致命的癌症。这一重要公共卫生问题的初级预防是可行的，因为它在很大程度上受到营养和药理学因素的影响，如膳食脂肪、纤维、微量营养素（即钙和硒）、阿司匹林和其他非甾体抗炎药。舒林达克是一种有效的结直肠癌化学预防剂。槲皮素，一种具有抗炎特性的植物源化合物，在临床前研究中抑制结肠癌的发展。然而，它在预防人类结直肠癌方面的有效性尚不清楚。非甾体抗炎药调节结肠上皮细胞的周转（诱导细胞静止和凋亡）。这一效应可能是其作为结肠癌化学预防剂的重要作用。本研究的目的是确定舒林酸和槲皮素对人结肠上皮细胞周转的影响。通过比较和对比这两种化合物对人类结肠细胞的影响，我们希望开始了解非甾体抗炎药化合物对人类结肠隐窝生理学的影响。通过这些和未来的研究，我们最终希望预测槲皮素作为结肠癌化学预防剂的潜在效用，并进一步阐明抗炎剂预防结肠癌发生的机制。