Anguilla japonica lectin 1 delivery through adenovirus vector induces apoptotic cancer cell death through interaction with PRMT5.

Abstract

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. 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. 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. 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.