Peroxidase from foxtail millet bran exerts anti-colorectal cancer activity via targeting cell-surface GRP78 to inactivate STAT3 pathway.
10.1016/j.apsb.2021.10.004
- Author:
Shuhua SHAN
1
;
Jinping NIU
1
;
Ruopeng YIN
1
;
Jiangying SHI
1
;
Lizhen ZHANG
2
;
Caihong WU
1
;
Hanqing LI
2
;
Zhuoyu LI
1
Author Information
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.
- Publication Type:Journal Article
- Keywords:
CAC, colitis-associated carcinogenesis;
CDKs, cyclin-dependent kinases;
CETSA, cellular thermal shift assay;
CRC, colorectal cancer;
Co-IP, co-immunoprecipitation;
Colorectal cancer;
DCFH-DA, dichloro-dihydro-fluorescein diacetate;
EGFR, epidermal growth factor receptor;
ER, endoplasmic reticulum;
FDA, U.S. Food and Drug Administration;
FMBP;
FMBP, peroxidase derived from foxtail millet bran;
Foxtail millet bran;
GRP78, glucose-regulated protein 78;
H&E, hematoxylin & eosin;
ISM, isthmin;
MPs, membrane proteins;
NBD, the nucleotide binding domain of csGRP78;
PD-1, programmed death-1;
ROS;
ROS, reactive oxygen species;
SBD, substrate-binding domain of csGRP78;
SPF, specific pathogen free;
STAT3;
STAT3, signal transducer and activator of transcription 3;
TRAIL, tumor necrosis factor-related apoptosis-inducing ligand;
csGRP78;
csGRP78, cell surface glucose-regulated protein 78;
rGRP78, recombinant GRP78
- From:
Acta Pharmaceutica Sinica B
2022;12(3):1254-1270
- CountryChina
- Language:English
-
Abstract:
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.
