title: Reconstructed mung bean trypsin inhibitor targeting cell surface GRP78 induces apoptosis and inhibits tumor growth in colorectal cancer.
abstract: Glucose regulated protein 78 (GRP78) has been reported to be present on cell membranes of cancer cells but not the normal cells, serving as a potential anti-cancer target. In the present study, a fusion protein containing the GRP78 binding peptide WIFPWIQL and the active fragment of mung bean trypsin inhibitor was constructed, and its targeted anti-tumor effects were investigated both in vitro and in vivo. The results showed that the fusion protein specifically inhibited growth and induced apoptosis in colorectal cancer cells but not in the normal cells. Mechanistically, these anti-tumor effects were attributed to induction of G1 phase arrest and activation of multiple apoptotic pathways. Importantly, the fusion protein could also suppress the growth of xenografted human colorectal carcinoma in vivo. Our study reveals that this fusion protein may be developed as a therapeutic agent for treatment of colon cancer, and holds important implications for developing other anti-cancer peptide drugs.
authors: Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan 030006, China. Electronic address: zongweili@sxu.edu.cn.
authors: Zongwei
authors: Z
authors: Li
authors: Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan 030006, China.
authors: Chao
authors: C
authors: Zhao
authors: Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan 030006, China; College of Life Science, Zhejiang Chinese Medical University, Hangzhou 310053, China. Electronic address: lzy@sxu.edu.cn.
authors: Zhuoyu
authors: Z
authors: Li
authors: Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan 030006, China.
authors: Yarui
authors: Y
authors: Zhao
authors: Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan 030006, China.
authors: Shuhua
authors: S
authors: Shan
authors: Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of Education, Shanxi University, Taiyuan 030006, China.
authors: Tonglin
authors: T
authors: Shi
authors: China Institute for Radiation Protection, Taiyuan 030006, China.
authors: Jianguo
authors: J
authors: Li
mesh_terms: D000818:Animals; D017209:Apoptosis; D048708:Cell Growth Processes / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000091342:Endoplasmic Reticulum Chaperone BiP; D007887:Fabaceae / Q000378:metabolism; D005260:Female; D019073:HT29 Cells; D006360:Heat-Shock Proteins / Q000235:genetics / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000494:pharmacology*; D014361:Trypsin Inhibitors / Q000235:genetics / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D011993:Recombinant Fusion Proteins; D014361:Trypsin Inhibitors
keywords: Colon cancer; GRP78; Targeted anti-tumor effect; Trypsin inhibitor