Induction of apoptosis by Polygonatum odoratum lectin and its molecular mechanisms in murine fibrosarcoma L929 cells.

BACKGROUND: The Galanthus nivalis agglutinin (GNA)-related lectins have been reported to bear antiproliferative and apoptosis-inducing activities in cancer cells; however, the precise mechanisms by which GNA-related lectins induce cell death are still only rudimentarily understood. METHODS: In the present study, Polygonatum odoratum lectin (designated POL), a mannose-binding specific GNA-related lectin, possessed a remarkable antiproliferative activity toward murine fibrosarcoma L929 cells. And, this lectin induced L929 cell apoptosis in a caspase-dependent manner. In addition, POL treatment increased the levels of FasL and Fas-Associated protein with Death Domain (FADD) proteins and resulted in caspase-8 activation. Also, POL treatment caused mitochondrial transmembrane potential collapse and cytochrome c release, leading to activations of caspase-9 and caspase-3. Moreover, POL treatment enhanced tumor necrosis factor alpha (TNFalpha)-induced L929 cell apoptosis. RESULTS: Our data demonstrate for the first time that this lectin induces apoptosis through both death-receptor and mitochondrial pathways, as well as amplifies TNFalpha-induced L929 cell apoptosis. GENERAL SIGNIFICANCE: These inspiring findings would provide new molecular basis for further understanding cell death mechanisms of the Galanthus nivalis agglutinin (GNA)-related lectins in future cancer investigations.

Induction of apoptosis by Concanavalin A and its molecular mechanisms in cancer cells.

Concanavalin A (Con A), a mannose/glucose-binding legume lectin, can induce cancer cell death through a mitochondria-mediated autophagic pathway; however, the precise mechanisms by which it mediates cell death are still only rudimentarily understood. In the present study, Con A possesses a remarkable antiproliferative effect on human melanoma A375 cells. Also, there is a link between the antiproliferative activity of Con A and its sugar-binding activity. Subsequently, Con A can induce human melanoma A375 cell apoptosis in a caspase-dependent manner. In addition, the treatment with Con A can cause mitochondrial transmembrane potential collapse, leading to cytochrome c release and caspase-9-caspase-3 activation. In conclusion, we demonstrate that there may be a close correlation between the antiproliferative activity of Con A and its sugar-binding activity. More importantly, we report for the first time that Con A can induce human melanoma A375 cell death in a caspase-dependent manner as well as via a mitochondrial apoptotic pathway.

Antiproliferative activity and apoptosis-inducing mechanism of Concanavalin A on human melanoma A375 cells.

The objective of this study was to investigate the antiproliferative activity and apoptosis-inducing mechanism of Concanavalin A (ConA) on human melanoma A375 cells. We firstly simulated the three-dimensional structure of ConA. Subsequently, we found that ConA possessed remarkable antiproliferative effect on A375 cells. Further experimental data indicated that there was a link between its hemagglutinating activity, mannose-binding activity and antiproliferative activity. In addition, we showed that ConA induced A375 cell apoptosis in a caspase-dependent manner. Then, we demonstrated that the treatment of ConA caused mitochondrial transmembrane potential (MMP) collapse, cytochrome c release and caspase activation. In conclusion, we report for the first time that there may be a close correlation between carbohydrate-binding activity of ConA and its antiproliferative activity. Also, we demonstrate firstly that ConA induces A375 cell death in a caspase-dependent manner as well as through a mitochondrial apoptotic pathway.

Apoptosis-inducing effect and structural basis of Polygonatum cyrtonema lectin and chemical modification properties on its mannose-binding sites.

Polygonatum cyrtonema Lectin (PCL), which is classified as a monocot mannose-binding lectin, has received great regards for its uniquely biological activities and potentially medical applications in cancer cells. This paper was initially aimed to study apoptosis of PCL on Hela cells. Thus, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) method was carried out. Through observation of cell morphologic changes and Lactate dehydrogenase (LDH) activity-based cytotoxicity assays, PCL induced HeLa cell apoptosis in a dose-dependent manner. To further gain structural basis, multiple alignments, homology modeling and docking experiments were performed to analyze the correlation between its biological activities and mannose-binding sites. Eventually, considering docking data, chemical modification properties on the three mannose-binding sites were analyzed by a series of biological experiments (e.g., hemagglutinating and mitogenic activity assays, fluorescence and Circular Dichrosim (CD) spectroscopy) to profoundly identify the role of some key amino acids in the structure-function relationship of PCL.

A mannose-binding lectin from Sophora flavescens induces apoptosis in HeLa cells.

The objective of this study was to investigate the anti-tumor activity of a lectin from Sophora flavescens and explore its potential apoptotic induction mechanism. Here, an elegant series of biochemical and cell biology methods were carried out in a sequential procedure (e.g., MTT, cell morphologic changes and LDH assays, DNA ladder as well as flow cytometric assay). As a result, we found that this lectin shows a strong cytotoxicity against HeLa cells and induces apoptosis in a time- and dose-dependent manner. Subsequently, according to caspase inhibition and Western blot analysis, we further demonstrated that it is a typical caspase-dependent apoptotic mechanism. Furthermore, we also exerted some bioinformatics methods to identify the mannose-binding specificity of this lectin. In conclusion, all experimental results demonstrated that this lectin seems to be a potent anti-tumor agent for its cytotoxicity and apoptosis effects on HeLa cells. Also, bioinformatics analyses showed that this lectin is speculated to bind a certain mannose-containing receptor on cancer cell surface thereby initiating downstream caspase cascade.