Abstract
Lectins exist widely in marine bioresources such as bacteria, algae, invertebrate animals and fishes. Some purified marine lectins have been found to elicit cytotoxicity to cancer cells. However, there are few reports describing the cytotoxic effect of marine lectins on cancer cells through virus-mediated gene delivery. We show here that a replication-deficient adenovirus-carrying gene encoding Haliotis discus discus sialic acid binding lectin (Ad.FLAG-HddSBL) suppressed cancer cell proliferation by inducing apoptosis, as compared to the control virus Ad.FLAG. A down-regulated level of anti-apoptosis factor Bcl-2 was suggested to be responsible for the apoptosis induced by Ad.FLAG-HddSBL infection. Further subcellular localization studies revealed that HddSBL distributed in cell membrane, ER, and the nucleus, but not in mitochondria and Golgi apparatus. In contrast, a previously reported mannose-binding lectin Pinellia pedatisecta agglutinin entered the nucleus as well, but did not distribute in inner membrane systems, suggesting differed intracellular sialylation and mannosylation, which may provide different targets for lectin binding. Further cancer-specific controlling of HddSBL expression and animal studies may help to provide insights into a novel way of anti-cancer marine lectin gene therapy. Lectins may provide a reservoir of anti-cancer genes.
Highlights
Lectins are carbohydrate-binding proteins which have become useful tools for recognizing a variety of cell types due to their carbohydrate recognition specificity [1,2]
To evaluate the cytotoxic effect of exogenous Haliotis discus discus sialic acid binding lectin (HddSBL), cancer cells including hepatocellular carcinoma cell line Hep3B, lung cancer cell lines A549 and H1299, as well as colorectal carcinoma cell line SW480 were treated with Ad.FLAG-HddSBL or the control adenovirus Ad.FLAG
Data indicated the cytotoxicity of exogenous HddSBL on various cancer cells, and the differential effect of HddSBL may be due to varied forms of intracellular sialic acids modification
Summary
Lectins are carbohydrate-binding proteins which have become useful tools for recognizing a variety of cell types due to their carbohydrate recognition specificity [1,2]. Some lectins such as Maackia amurensis seed lectin [3], Concanavalin A [4], and Polygonatum cyrtonema lectin [5]. Most studies of SBLs were performed in animal adhesion molecules Siglecs [8], which are expressed on the cell membrane of various immune cells including macrophages [9,10], B cells [11], neutrophils [12], as well as some cancer cells [13,14]. To analyze the underlying mechanism of the HddSBL induced cytotoxicity, the subcellular distribution of HddSBL in cancer cells was investigated through transfection of cells with plasmid pEGFP-HddSBL-C1, followed by observation under a confocal laser scanning microscope
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