Inhibitory Effects of Peroxidase from Foxtail Millet Bran on Colitis-Associated Colorectal Carcinogenesis by the Blockage of Glycerophospholipid Metabolism

Abstract

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.

Hypoxia-related lncRNA Signature to Predict the Survival of Patients with Clear Cell Renal Cell Carcinoma

“…Since homologous recombination-de cient cells are sensitive to poly(ADP-ribose) polymerase (PARP) inhibitors, they have attracted clinical interest (31). Abnormal glycerophospholipid (GPL) metabolism is a common metabolic hallmark of cancer and is associated with tumor progression, which is represented by phosphatidylethanolamine (PE) and phosphatidylcholine (PC) (32). Some studies have shown elevated PC levels in most cancers, including brain(33, 34), breast (35, 36), ovarian (37), cervical(38), endometrial (39) and prostate(40) cancers.…”

OMICS Applications for Medicinal Plants in Gastrointestinal Cancers: Current Advancements and Future Perspectives

“…Chronic inflammation caused by inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, plays a critical role in tumorigenesis of the gastrointestinal tract (Lichtenstern et al, 2020). Mechanistically, DNA hypermethylation, reactive oxygen species (ROS) production and gut microbiota imbalance facilitate IBD, subsequently leading to the initiation and progression of colitisassociated carcinogenesis (CAC) (Rogler, 2014;Gagnière et al, 2016) The results speculated that FMBP blocked GPL metabolism by reducing the expression levels of key metabolic enzymes involved in phosphatidylcholine and phosphatidylethanolamine (such as PCYT1α and PCYT2), resulting in insufficient adenosine triphosphate to maintain CRC growth (Shan et al, 2020).…”

Fermented and Germinated Processing Improved the Protective Effects of Foxtail Millet Whole Grain Against Dextran Sulfate Sodium-Induced Acute Ulcerative Colitis and Gut Microbiota Dysbiosis in C57BL/6 Mice

“…Along with its superior nutritional properties and documented anti-inflammatory function, foxtail millet is also rich in non-nutrient prebiotics, such as polyphenols and dietary fibers ( 22 ), suggesting its possible positive effects on the gut microbiota and IBD. Bond polyphenols and peroxidase of foxtail millet bran have also been reported to inhibit colitis-induced carcinogenesis in a mouse model ( 23 , 24 ).…”