Peroxidase from foxtail millet bran exerts anticolorectal cancer activity via targeting cellsurface GRP78 to inactivate STAT3 pathway  

作　　者：Shuhua Shan Jinping Niu Ruopeng Yin Jiangying Shi Lizhen Zhang Caihong Wu Hanqing Li Zhuoyu Li 

机构地区：[1]Institute of Biotechnology,Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education,Shanxi University,Taiyuan 030006,China [2]School of Life Science,Shanxi University,Taiyuan 030006,China

出　　处：《Acta Pharmaceutica Sinica B》2022年第3期1254-1270,共17页药学学报（英文版）

基　　金：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.XCSXUKF-202004,China)。

摘　　要：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(cs GRP78)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 cs GRP78interfered 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 cs GRP78 acts as an underlying target of FMBP against CRC,uncovering the clinical potential of FMBP as a targeted agent for CRC in the future.

关 键 词：Foxtail millet bran FMBP csGRP78 STAT3 ROS Colorectal cancer 

分 类 号：R285[医药卫生—中药学]