Exogenous expression of marine lectins DlFBL and SpRBL induces cancer cell apoptosis possibly through PRMT5-E2F-1 pathway

Abstract

Lectins are widely existed in marine bioresources, and some purified marine lectins were found toxic to cancer cells. In this report, genes encoding Dicentrarchus labrax fucose-binding lectin (DlFBL) and Strongylocentrotus purpuratus rhamnose-binding lectin (SpRBL) were inserted into an adenovirus vector to form Ad.FLAG-DlFBL and Ad.FLAG-SpRBL, which elicited significant in vitro suppressive effect on a variety of cancer cells. Anti-apoptosis factors Bcl-2 and XIAP were determined to be downregulated by Ad.FLAG-DlFBL and Ad.FLAG-SpRBL. Subcellular localization studies showed that DlFBL but not SpRBL widely distributed in membrane systems. Both DlFBL and SpRBL were shown associated with protein arginine methyltransferase 5 (PRMT5), and PRMT5-E2F-1 pathway was suggested to be responsible for the DlFBL and SpRBL induced apoptosis. Further investigations revealed that PRMT5 acted as a common binding target for various exogenous lectin and non-lectin proteins, suggesting a role of PRMT5 as a barrier for foreign gene invasion. The cellular response to exogenous lectins may provide insights into a novel way for cancer gene therapy.

Ulva pertusa lectin 1 delivery through adenovirus vector affects multiple signaling pathways in cancer cells

“…Previously, plasmid pEGFP-UPL1-C1 was cotransfected into BEL-7404 or Hep3B cells with pdsRed-PRMT5, and the colocalization of UPL1 tagged with EGFP and PRMT5 tagged with red fluorescent protein dsRed has been shown under a confocal laser scanning microscope [12]. Here, we further confirm the interaction of UPL1 with PRMT5 through immunoprecipitation and Western blotting analysis.…”

“…The varied distribution of exogenous lectins may reflect varied subcellular glycosylation patterns, thus providing binding sites for different lectins. Our studies also showed that exogenous lectins including PPA, DlFBL, SpRBL, AJL1, HddSBL [11][12][13][14] as well as UPL1 induced varied intracellular signaling pathways. Taken together, varied intracellular signaling pathways affected by Fig.…”

“…The distribution of UPL1 in cell membrane, ER, and mitichondria, but not Golgi apparatus, was observed. Previously, the intracellular distribution of various exogenous lectins has been investigated in our laboratory [12][13][14]. Exogenous fucose binding lectin DlFBL was shown to be distributed in various membrane systems, including cell membrane, mitichondria, ER, and Golgi apparatus in cancer cells.…”

“…Previously, we determined that, through adenovirus-mediated gene delivery, lectins including mannose binding plant lectin Pinellia pedatisecta agglutinin (PPA) as well as marine lectins such as galectin Anguilla japonica lectin 1 (AJL1), Haliotis discus discus sialic acid binding lectin (HddSBL), Dicentrarchus labrax fucose binding lectin (DlFBL), and Strongylocentrotus purpuratus rhamnose binding lectin (SpRBL) elicited cytotoxicity to a variety of cancer cells [11][12][13][14]. Protein arginine methyltransferase 5 (PRMT5) was determined to act as a common binding target for exogenous PPA, DlFBL, SpRBL, HddSBL, as well as AJL1.…”

Crystal structure of MytiLec, a galactose-binding lectin from the mussel Mytilus galloprovincialis with cytotoxicity against certain cancer cell types

“…Exogenous expression of some lectins derived from marine sources has been shown to induce apoptosis in cancer cells11, but the marked cytotoxicity of many lectins substantially reduces the possibility of developing them into clinically useful formulations. The lectin ABL, from the edible mushroom Agaricus bisporus , combines both strong antiproliferative effects on epithelial cancer cells with no apparent cytotoxicity to normal cells1213.…”