Polygonatum cyrtonema lectin (PCL), a mannose/sialic acid-binding plant lectin, has recently drawn a rising attention for cancer biologists because PCL bears remarkable anti-tumor activities and thus inducing programmed cell death (PCD) including apoptosis and autophagy in cancer cells. In this review, we focus on exploring the precise molecular mechanisms by which PCL induces cancer cell apoptotic death such as the caspase-dependent pathway, mitochondria-mediated ROS-p38-p53 pathway, Ras-Raf and PI3K-Akt pathways. In addition, we further elucidate that PCL induces cancer cell autophagic death via activating mitochondrial ROS-p38-p53 pathway, as well as via blocking Ras-Raf and PI3K-Akt pathways, suggesting an intricate relationship between autophagic and apoptotic death in PCL-induced cancer cells. In conclusion, these findings may provide a new perspective of Polygonatum cyrtonema lectin (PCL) as a potential anti-tumor drug targeting PCD pathways for future cancer therapeutics.

Polygonatum cyrtonema lectin (PCL) has been drawing rising attention due to its remarkable bioactivities. Whereas, large-scale isolation and purification of PCL from Polygonatum cyrtonema Hua is not feasible due to the extremely low propagation rate of this plant. Herein, an alternative method to produce large amount of PCL by Escherichia coli expression system was proposed, and recombinant Polygonatum cyrtonema lectin (rPCL) was successfully obtained under the optimized conditions (OD600=0.6, 30◦C, 0.5mM IPTG, pH 7.2). Subsequent SDS-PAGE and MALDI-TOF analysis confirmed that the molecular mass of rPCL was approximate to 12 kDa. After further identification of rPCL by Western blot and N-terminal amino acid sequence analysis, the comparisons of hemagglutinating and carbohydrate-binding activities as well as the anti-viral and apoptosis-inducing properties between rPCL and native Polygonatum cyrtonema lectin (nPCL) were made. It was verified that the bioactivities of rPCL were relatively weaker than that of nPCL. Moreover, for future exploring three-dimensional structure and structure–bioactivity relationship of rPCL, circular dichroism and fluorescence spectroscopy, preliminary crystallization and X-ray diffraction were determined. Taken together, these findings provide novel evidence that rPCL could replace nPCL as a potential anti-tumor and anti-viral protein in possible medical application and large-scale pharmaceutical industry.

It is well-known that cell cycle arrest and/or death play a pivotal role in tumor progression, which has drawn a rising attention for cancer biologists due to their complex and intricate relationships. In this review, we demonstrate the recent research on oridonin, an active diterpenoid with remarkable antiproliferative activities, and then further explore its molecular mechanisms of cell cycle arrest, apoptosis, autophagy and their cross-talks in various cancer cells, which may provide a new perspective of oridonin as a candidate anti-neoplastic drug for future cancer therapeutics.

The Galanthus nivalis agglutinin (GNA)-related lectin family exhibit significant anti-HIV and anti-HSV properties that are closely related to their carbohydratebinding activities. However, there is still no conclusive evidence that GNA-related lectins possess anti-influenza properties. The hemagglutinin (HA) of influenza virus is a surface protein that is involved in binding host cell sialic acid during the early stages of infection. Herein, we studied the 3D-QSARs (three-dimensional quantitative structure-activity relationships) of lectin-and HA-sialic acid by molecular modeling. The affinities and stabilities of lectin-and HA-sialic acid complexes were also assessed by molecular docking and molecular dynamics simulations. Finally, anti-influenza GNA-related lectins that possess stable conformations and higher binding affinities for sialic acid than HAs of human influenza virus were screened, and a possible mechanism was proposed. Accordingly, our results indicate that some GNA-related lectins, such as Yucca filamentosa lectin and Polygonatum cyrtonema lectin, could act as drugs that prevent influenza virus infection via competitive binding. In conclusion, the GNArelated lectin family may be helpful in the design of novel candidate agents for preventing influenza A infection through the use of competitive combination against sialic acid specific viral infection.

Polygonatum odoratum lectin (POL), a novel mannose-binding lectin with anti-viral and apoptosisinducing activities, was isolated from rhizomes of Polygonatum odoratum (Mill.) Druce. POL was a homo-tetramer with molecular weight of 11953.623 Da per subunits as determined by gel filtration, SDS-PAGE and mass spectrometry. Based on its N-terminal 29-amino acid sequence the full-length cDNA sequence of POL was cloned. Subsequent phylogenetic analysis and molecular modeling revealed that POL belonged to the Galanthus nivalis agglutinin (GNA)-related lectin family, which acquired unique mannose-binding specificity. The hemagglutinating activities of POL were metal ion-independent, and were stable within certain range of pH and temperature alterations. Moreover, POL showed remarkable anti-HSV-II activity towards Vero cells, cytotoxicity towards human melanoma A375 cells and induced apoptosis in a caspase-dependent manner.