Inhibitory Effects of Peroxidase from Foxtail Millet Bran on Colitis-Associated Colorectal Carcinogenesis by the Blockage of Glycerophospholipid Metabolism
Inhibitory Effects of Peroxidase from Foxtail Millet Bran on Colitis-Associated Colorectal Carcinogenesis by the Blockage of Glycerophospholipid Metabolism
复制标题
谷子麸皮过氧化物酶通过阻断甘油磷脂代谢对结肠炎相关结直肠癌发生的抑制作用
DOI：
10.1021/acs.jafc.0c03257
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发表时间：
2020-08-05
影响因子：
6.1
通讯作者：
Li, Zhuoyu
中科院分区：
文献类型：
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作者：
Shan, Shuhua;Wu, Caihong;Li, Zhuoyu
以磷脂酰胆碱(PC)和磷脂酰乙醇胺(PE)为代表的甘油磷脂(GPL)代谢异常已成为肿瘤的普遍代谢标志，参与肿瘤的进展。我们先前的发现表明，小米麸皮过氧化物酶(FMBP)在体外和裸鼠体内具有显著的抗结直肠癌(CRC)活性。目前，通过偶氮甲烷(AOM)/葡聚糖硫酸钠(DSS)诱导的小鼠结肠炎相关癌变(CAC)模型，进一步评价了FMBP的临床应用潜力，揭示了GPL代谢在FMBP抗结直肠癌作用中的关键作用。令人兴奋的是，FMBP能显著减少小鼠CAC息肉的数量和体积，有效改善CAC小鼠的生理指标。同时，FMBP可有效抑制CAC小鼠早期结直肠癌标志物(环氧合酶2、肿瘤增殖核抗原Ki-67和EGF模块粘蛋白样受体1)的表达。代谢组学分析表明，经FMBP处理的CAC小鼠体内参与GPL代谢的PC和PE的含量显著减少，这一点在人CRC细胞中也得到了证实。此外，FMBP降低了PE和PC关键代谢酶的表达水平，导致GPL代谢受阻，三磷酸腺苷不足以维持CRC的生长。总体而言，FMBP通过阻断GPL代谢，有可能成为CRC的预防和治疗候选药物。
Abnormal glycerophospholipid (GPL) metabolism represented by phosphatidylcholine (PC) and phosphatidylethanolamine (PE) has been as a universal metabolic hallmark of cancer, which is involved in tumor progression. Our previous finding showed that peroxidase from foxtail millet bran (FMBP) exhibited significant anticolorectal cancer (CRC) activity in vitro and in nude mice. Presently, the potential of FMBP in clinical application was further evaluated by an azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colitis-associated carcinogenesis (CAC) mice model, revealed the pivotal role of GPL metabolism in anti-CRC effects of FMBP. Excitedly, FMBP significantly reduced the number and volume of CAC polyps of mice and effectively improved physiological indexes of CAC mice. Meanwhile, the elevated expressions of CRC early markers (cyclooxygenase 2, tumorproliferating nuclear antigen Ki-67, and EGF module-containing mucin-like receptor 1) in CAC mice were efficiently prevented by FMBP treatment. Metabolomics analysis showed that the elevated abundances of PC and PE involved in GPL metabolism in CAC mice were markedly decreased in FMBP-treated groups, which was also verified in human CRC cells. Further, FMBP reduced the expression levels of PE and PC key metabolic enzymes, resulting in the blockage of GPL metabolism and insufficient adenosine triphosphate to maintain CRC growth. Collectively, FMBP has the potential as a preventive and therapeutic candidate for CRC through the blockage of GPL metabolism.