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Anguilla japonica lectin 1 delivery through adenovirus vector induces apoptotic cancer cell death through interaction with PRMT5
Author(s) -
Li Gongchu,
Gao Yajun,
Cui Lianzhen,
Wu Liqin,
Yang Xinyan,
Chen Jing
Publication year - 2016
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.2878
Subject(s) - biology , protein kinase a , kinase , cancer cell , microbiology and biotechnology , protein arginine methyltransferase 5 , e2f , apoptosis , cell cycle , biochemistry , cancer , gene , methylation , methyltransferase , genetics
Background Our previous studies have demonstrated that, through adenovirus mediated gene delivery, various exogenously expressed lectins elicited cytotoxicity to cancer cells, utilizing protein arginine methyltransferase 5 (PRMT5) as a common binding target. Methods In the present study, a FLAG tagged Anguilla japonica lectin 1 (AJL1) expression cassette was genetically harbored in a replication‐defective adenovirus genome, forming Ad.FLAG‐AJL1. The exogenous AJL1‐induced cytotoxicity and the underlying mechanisms were analyzed. Results The exogenous AJL1 suppressed the proliferation of a variety of human cancer cells by inducing apoptosis. Caspase 9, Bcl‐2, X‐linked inhibitor of apoptosis protein, mitogen‐activated protein kinase kinase 1/2‐extracellular signal‐regulated kinase and p38 mitogen‐activated protein kinase were found to be responsible for the exogenous AJL1‐induced cytotoxicity. AJL1 was further suggested to regulate PRMT5‐E2F‐1 pathway, a pathway shared by previously reported marine lectins Dicentrarchus labrax fucose binding lectin and Strongylocentrotus purpuratus rhamnose binding lectin. A localization study revealed that exogenous AJL1 widely distributed in the cell membrane and cytoplasm. Conclusions The results of the present study suggest that the PRMT5‐E2F‐1 pathway may act as a common target for exogenous lectins including AJL1, and the cellular response to exogenous AJL1 may suggest a novel agent for cancer gene therapy. Copyright © 2016 John Wiley & Sons, Ltd.