期刊
FREE RADICAL BIOLOGY AND MEDICINE
卷 177, 期 -, 页码 156-166出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2021.10.022
关键词
Ferroptosis; Colitis-associated carcinogenesis; High-fat diet; CHAC1; Endoplasmic reticulum stress
资金
- National Nature Science Foundation of China [81672891, 81970467]
- CAMS Innovation Fund for Medical Sciences (CIFMS) [2016-I2M-1-001, 2017-I2M-1-006, 2019-I2M-1-003]
- State key laboratory of molecular oncology
A high-fat diet exacerbates colorectal cancer by suppressing lipid peroxidation and iron-dependent cell death, known as ferroptosis. Ferroptosis is negatively correlated with tumor number in colorectal cancer. A lipid mixture can block ferroptosis, offering a new potential approach for colorectal cancer prevention.
Ferroptosis, a type of programmed cell death caused by lipid peroxidation has recently been observed in colitis. Whether a high-fat diet (HFD) affects ferroptosis and whether it contributes to colitis-associated carcinogenesis (CAC) has not been explored. We found iron, lipid peroxidation, and ferroptotic markers to be elevated in AOM/ DSS (azoxymethane/dextran sulfate sodium)-induced mouse CAC model. Transmission electron microscopy also confirmed the occurrence of ferroptosis in colonic tissues. Treatment with the ferroptosis inhibitor, ferrostatin-1 increased the incidence of CAC. Compared with iso-caloric control mice, HFD mice exhibited increased tumor number and a higher degree of dysplasia following repression of lipid peroxidation and ferroptosis marker expression in mouse colon tissue. Furthermore, ferroptosis markers were negatively correlated with the tumor number in mice. In vitro, a lipid mixture blocked ferroptosis in various colorectal cancer cell lines and inhibited GSH degradation by negatively regulating CHAC1, a target in ER stress signaling. Finally, the ferroptosis inducer partly abolished the pro-tumor effect of the HFD on CAC in vivo. Collectively, these findings suggest that a HFD aggravates CAC through the evasion of ferroptosis in the ER stress-mediated pathway and provide a new perspective for CAC prevention in the future.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据