Original articles
Shuhua Shan, Jinping Niu, Ruopeng Yin, Jiangying Shi, Lizhen Zhang, Caihong Wu, Hanqing Li, Zhuoyu Li. Peroxidase from foxtail millet bran exerts anti-colorectal cancer activity via targeting cell-surface GRP78 to inactivate STAT3 pathway[J]. Acta Pharmaceutica Sinica B, 2022, 12(3): 1254-1270

Peroxidase from foxtail millet bran exerts anti-colorectal cancer activity via targeting cell-surface GRP78 to inactivate STAT3 pathway
Shuhua Shana, Jinping Niua, Ruopeng Yina, Jiangying Shia, Lizhen Zhangb, Caihong Wua, Hanqing Lib, Zhuoyu Lia,b
a. Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan 030006, China;
b. School of Life Science, Shanxi University, Taiyuan 030006, China
Molecular targeted therapy has become an emerging promising strategy in cancer treatment, and screening the agents targeting at cancer cell specific targets is very desirable for cancer treatment. Our previous study firstly found that a secretory peroxidase of class III derived from foxtail millet bran (FMBP) exhibited excellent targeting anti-colorectal cancer (CRC) activity in vivo and in vitro, whereas its underlying target remains unclear. The highlight of present study focuses on the finding that cell surface glucose-regulated protein 78 (csGRP78) abnormally located on CRC is positively correlated with the anti-CRC effects of FMBP, indicating it serves as a potential target of FMBP against CRC. Further, we demonstrated that the combination of FMBP with the nucleotide binding domain (NBD) of csGRP78 interfered with the downstream activation of signal transducer and activator of transcription 3 (STAT3) in CRC cells, thus promoting the intracellular accumulation of reactive oxygen species (ROS) and cell grown inhibition. These phenomena were further confirmed in nude mice tumor model. Collectively, our study highlights csGRP78 acts as an underlying target of FMBP against CRC, uncovering the clinical potential of FMBP as a targeted agent for CRC in the future.
Key words:    Foxtail millet bran    FMBP    csGRP78    STAT3    ROS    Colorectal cancer   
Received: 2021-06-10     Revised: 2021-08-31
DOI: 10.1016/j.apsb.2021.10.004
Funds: This study was supported by National Natural Science Foundation of China (Nos. 31500630, 31770382, 32072220, and 81803238); "1331 Project" Key Innovation Center and Team, National Key Research and Development Project (No. 2020YFD1001405, China); Shanxi Key Laboratory for Research and Development of Regional Plants, Higher Education Institution Project of Shanxi Province:Ecological Remediation of Soil Pollution Disciplines Group (No. 20181401, China); the Open Project Program of Xinghuacun College of Shanxi University[Shanxi Institute of Brewing Technology and Industry (Preparation)] (No. XCSXU-KF-202004, China).
Corresponding author: Zhuoyu Li,E-mai:lzy@sxu.edu.cn     Email:lzy@sxu.edu.cn
Author description:
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Shuhua Shan
Jinping Niu
Ruopeng Yin
Jiangying Shi
Lizhen Zhang
Caihong Wu
Hanqing Li
Zhuoyu Li

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