jf0c03257_si_001.pdf (555.21 kB)
Inhibitory Effects of Peroxidase from Foxtail Millet Bran on Colitis-Associated Colorectal Carcinogenesis by the Blockage of Glycerophospholipid Metabolism
journal contribution
posted on 2020-07-27, 11:37 authored by Shuhua Shan, Caihong Wu, Jiangying Shi, Xiaoli Zhang, Jinping Niu, Hanqing Li, Zhuoyu LiAbnormal
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.