Inhibitory Effects of Peroxidase from Foxtail Millet Bran on Colitis-Associated Colorectal Carcinogenesis by the Blockage of Glycerophospholipid Metabolism.,Journal of Agricultural and Food Chemistry

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Inhibitory Effects of Peroxidase from Foxtail Millet Bran on Colitis-Associated Colorectal Carcinogenesis by the Blockage of Glycerophospholipid Metabolism.
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2020-07-13 , DOI: 10.1021/acs.jafc.0c03257
Shuhua Shan ₁ , Caihong Wu ₁ , Jiangying Shi ₁ , Xiaoli Zhang ₁ , Jinping Niu ₁ , Hanqing Li ₂ , Zhuoyu Li _{1,

2}

Affiliation

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, tumor-proliferating 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.

中文翻译：

谷子麸皮过氧化物酶对结肠炎相关大肠癌发生的抑制作用（通过甘油磷脂代谢的阻滞）。

磷脂酰胆碱（PC）和磷脂酰乙醇胺（PE）代表的甘油磷脂异常（GPL）代谢已成为癌症的普遍代谢标志，与肿瘤的进展有关。我们之前的发现表明，谷子麸皮（FMBP）中的过氧化物酶在体外和裸鼠中均表现出显着的抗结直肠癌（CRC）活性。目前，通过甲氧甲烷（AOM）/右旋糖酐硫酸钠（DSS）诱导的结肠炎相关癌变（CAC）小鼠模型进一步评估了FMBP在临床中的潜力，揭示了GPL代谢在抗CRC作用中的关键作用。 FMBP。令人兴奋的是，FMBP显着减少了小鼠CAC息肉的数量和体积，并有效改善了CAC小鼠的生理指标。同时，CRC早期标志物（环氧合酶2，FMBP处理可有效预防CAC小鼠体内的肿瘤增殖核抗原Ki-67和含EGF模块的粘蛋白样受体1）。代谢组学分析表明，FMBP治疗组的CAC小鼠中参与GPL代谢的PC和PE的丰度明显降低，这在人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通过阻止GPL代谢而具有作为CRC的预防和治疗候选物的潜力。代谢组学分析表明，FMBP治疗组的CAC小鼠中参与GPL代谢的PC和PE的丰度明显降低，这在人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通过阻止GPL代谢而具有作为CRC的预防和治疗候选物的潜力。代谢组学分析表明，FMBP治疗组的CAC小鼠中参与GPL代谢的PC和PE的丰度明显降低，这在人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通过阻止GPL代谢而具有作为CRC的预防和治疗候选物的潜力。导致GPL代谢受阻，三磷酸腺苷不足以维持CRC生长。总体而言，FMBP通过阻止GPL代谢而具有作为CRC的预防和治疗候选物的潜力。导致GPL代谢受阻，三磷酸腺苷不足以维持CRC生长。总体而言，FMBP通过阻止GPL代谢而具有作为CRC的预防和治疗候选物的潜力。

更新日期：2020-08-05

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