DNA mismatch repair status may influence anti-neoplastic effects of butyrate
DNA mismatch repair status may influence anti-neoplastic effects of butyrate
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DOI：
10.1042/bst0330728
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发表时间：
2005-08-01
影响因子：
3.9
通讯作者：
Mathers, JC
中科院分区：
文献类型：
--
作者：
Coxhead, JM;Williams, EA;Mathers, JC
HNPCC（遗传性非息肉病性结肠癌）是一种常染色体显性遗传疾病，其特征为早发性 CRC（结直肠癌）。 HNPCC 通常与 MMR（错配修复）基因 hMLH1、hMSH2、hMSH6 或 hPMS2 的突变有关。有缺陷的 MMR 系统的突变表型是 MS1（微卫星不稳定性），这种情况也发生在大约 10 年内。 15-25% 的散发性 CRC 病例与 hMLH1 启动子区域的高甲基化有关。饮食因素，包括过量饮酒、摄入红肉和叶酸摄入量低，可能会增加 MS1 高投票率发生的风险。相反，阿司匹林可能会抑制 MMR 缺陷的 CRC 细胞系中的 MSI。丁酸盐是结肠中碳水化合物发酵的短链脂肪酸终产物，与阿司匹林具有许多相同的抗肿瘤特性，包括抑制结直肠癌细胞的增殖和诱导细胞凋亡。最近的体外研究表明，生理浓度的丁酸盐（0.5-2 mM）可能对缺乏 MMR 的 CRC 细胞系具有更有效的抗肿瘤作用，但这种差异反应的机制仍有待建立。
HNPCC (hereditary non-polyposis colon cancer) is an autosomal-dominant disorder characterized by early-onset CRC (colorectal cancer). HNPCC is most often associated with mutations in the MMR (mismatch repair) genes hMLH1, hMSH2, hMSH6 or hPMS2. The mutator phenotype of a defective MMR system is MS1 (microsatellite instability), which also occurs in approx. 15-25% of sporadic CRC cases, where it is associated with the hypermethylation of the promoter region of hMLH1. Dietary factors, including excessive alcohol consumption, ingestion of red meat and low folate intake, may increase the risk of MS1 high turnout development. in contrast, aspirin may suppress MSI in MMR-deficient CRC cell lines. Butyrate, a short-chain-fatty-acid end product of carbohydrate fermentation in the colon, shares a number of anti-neoplastic properties with aspirin, including inhibiting proliferation and inducing apoptosis of CRC cells. Recent in vitro studies suggest that physiological concentrations of butyrate (0.5-2 mM) may have more potent antineoplastic effects in CRC cell lines deficient in MMR, but mechanisms for such a differential response remain to be established.