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: Zongwei Li, Chao Zhao, Zhuoyu Li, Yarui Zhao, Shuhua Shan, Tonglin Shi, Jianguo Li
• Journal: The international journal of biochemistry & cell biology (Int J Biochem Cell Biol) Vol. 47 Pg. 68-75 (Feb 2014) ISSN: 1878-5875 [Electronic] Netherlands
• PMID: 24333163 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• Endoplasmic Reticulum Chaperone BiP
• HSPA5 protein, human
• Heat-Shock Proteins
• Hspa5 protein, mouse
• Recombinant Fusion Proteins
• Trypsin Inhibitors

Topics

• Animals
• Apoptosis
• Cell Growth Processes (drug effects)
• Cell Survival (drug effects)
• Colorectal Neoplasms (drug therapy, metabolism, pathology)
• Endoplasmic Reticulum Chaperone BiP
• Fabaceae (metabolism)
• Female
• HT29 Cells
• Heat-Shock Proteins (genetics, pharmacology)
• Humans
• Mice
• Mice, Inbred NOD
• Mice, SCID
• Recombinant Fusion Proteins (genetics, pharmacology)
• Trypsin Inhibitors (genetics, pharmacology)
• Xenograft Model Antitumor Assays