Plant lectins, carbohydrate-binding proteins distributed widely in a variety of plant species, have drawn a rising attention for cancer biologists due to their remarkable anti-tumour properties. In this review, we present a brief outline of the up-to-date advances of plant lectins in elucidating their complex anti-cancer mechanisms implicated in apoptosis and autophagy. In addition, we further discuss the pre-clinical and clinical studies of plant lectins for their potential therapeutic applications. In conclusion, these inspiring findings would open a new perspective for plant lectins as potential antineoplastic drugs from bench to clinic.

A 48 kDa, chitin-binding lectin with antifungal, antiviral and apoptosis-inducing activities was isolated from the rhizomes of Setcreasea purpurea Boom, a member of family Commelinaceae. Setcreasea purpurea lectin (designated as SPL) is a homotetrameric protein consisting of 12031.9 Da subunits linked by noncovalent bonds as determined by SDS-PAGE, gel filtration and MS. The N-terminal 25 amino-acid sequence of SPL, NVLGRDAYCGSQNPGATCPGLCCSK was determined and homology analysis suggested that SPL belongs to the family of chitin-binding plant lectins composed of hevein domains. The lectin exhibited strong hemagglutinating activity towards rabbit erythrocytes at 0.95 g/ml and the activity could be reversed exclusively by chitin hydrolysate (oligomers of GlcNAc). Its hemagglutinating activity was stable in pH range of 2.0-9.0 and it showed excellent thermal tolerance. SPL showed antifungal activity against Rhizoctonia solani, Sclerotinia sclerotiorum, Penicillium italicum and Helminthosporiun maydis. It also exhibited inhibitory effect on HIV-1 (IIIB) and HIV-2 (ROD), with an EC50 of 13.8±1.3 and 57.1±15 g/ml, respectively. Subsequently, MTT method, cell morphological analysis and LDH activity-based cytotoxicity assays demonstrated that SPL was highly cytotoxic to CNE-1 cells and induced apoptosis in a dosedependent manner. Moreover, due to the caspase inhibitors analyses, caspase was also found to play an important role in the potential apoptotic mechanism of SPL.

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.

Polygonatum cyrtonema lectin (PCL) is a novel anti-HIV mannose-binding lectin from Galanthus nivalis agglutinin (GNA)-related lectin family. Crystal structures of ligand-free PCL and its complexes with monomannoside and a1-3 dimannoside have been determined. The ligand-free PCL is dimeric, with both subunits adopt the b-prism II fold. PCL subunit binds mannose using a potential bivalent mode instead of the usual trivalent mode, in which carbohydrate-binding site (CBS) I and CBS III adopt the conserved mannose-binding motif of QXDXNXVXY (X is one of any amino acid residues) as observed in other structurally characterized GNA-related lectins, while CBS II adopts a modified motif with residues Gln58 and Asp60, which are critical for mannose-binding, substituted by His58 and Asn60, respectively. As a result, CBS II is unfit for mannose-binding. In the mannoside complexes, ligand-bindings only occur at CBS I which provides the specificity for a1-3 dimannoside. CBS II and CBS III are cooperatively occupied by a well-ordered sulfate ion, through which the individual dimers are cross-linked to form a unique superstructure of 32 helical lattice. Surveying the sequences of GNA-related lectins revealed that the modified binding motif of CBS II is widely distributed in the Liliaceae family as an intrinsic structural element. There is evidence that other GNA-related lectins will also adopt the similar super-structure as PCL. Thus PCL structure, unique in ligand-binding mode, may represent a novel type of structure of GNA-related lectins. Comparative analyses indicated that the dimer-based super-structure may play a primary role in the anti-HIV property of PCL.

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.