Recent advances in the use of legume lectins for the diagnosis and treatment of breast cancer.

Poor lifestyle choices and genetic predisposition are factors that increase the number of cancer cases, one example being breast cancer, the third most diagnosed type of malignancy. Currently, there is a demand for the development of new strategies to ensure early detection and treatment options that could contribute to the complete remission of breast tumors, which could lead to increased overall survival rates. In this context, the glycans observed at the surface of cancer cells are presented as efficient tumor cell markers. These carbohydrate structures can be recognized by lectins which can act as decoders of the glycocode. The application of plant lectins as tools for diagnosis/treatment of breast cancer encompasses the detection and sorting of glycans found in healthy and malignant cells. Here, we present an overview of the most recent studies in this field, demonstrating the potential of lectins as: mapping agents to detect differentially expressed glycans in breast cancer, as histochemistry/cytochemistry analysis agents, in lectin arrays, immobilized in chromatographic matrices, in drug delivery, and as biosensing agents. In addition, we describe lectins that present antiproliferative effects by themselves and/or in conjunction with other drugs in a synergistic effect.

Homology modeling, molecular docking, and dynamics of two α-methyl-D-mannoside-specific lectins from Arachis genus.

The Arachis genus belongs to the Dalbergieae tribe, a group of plants that show promising potential novel lectins. Three lectins of the well-known Arachis hypogaea have already been purified, while lectins from related species are still unknown. Genomes of two closely related species, Arachis duranensis and Arachis ipaensis, were recently sequenced. Therefore, this study aimed to establish the three-dimensional structure of Arachis duranensis lectin (ADL) and Arachis ipaensis lectin (AIL) by homology modeling, test their activity against mannosides, and perform molecular dynamics (MD) simulations on these two proteins, both unligated and interacting with mannose or α-methyl-D-mannoside. The fold obtained for the molecular models agrees with data obtained from previous leguminous lectins, showing a conserved jelly roll motif. Docking scores indicate that these lectins have different theoretical binding energy with monosaccharides, disaccharides, and high-mannose glycans. MD simulations revealed that these proteins are α-methyl-D-mannoside-specific, having less stable interactions with mannose. This study thus serves as a guide for further research on lectins of the Arachis genus.

Structural analysis of Dioclea lasiocarpa lectin: A C6 cells apoptosis-inducing protein.

Lectins are multidomain proteins that specifically recognize various carbohydrates. The structural characterization of these molecules is crucial in understanding their function and activity in systems and organisms. Most cancer cells exhibit changes in glycosylation patterns, and lectins may be able to recognize these changes. In this work, Dioclea lasiocarpa seed lectin (DLL) was structurally characterized. The lectin presented a high degree of similarity with other lectins isolated from legumes, presenting a jelly roll motif and a metal-binding site stabilizing the carbohydrate-recognition domain. DLL demonstrated differential interactions with carbohydrates, depending on type of glycosidic linkage present in ligands. As observed by the reduction of cell viability in C6 cells, DLL showed strong antiglioma activity by mechanisms involving activation of caspase 3.

Purification and primary structure of a novel mannose-specific lectin from Centrolobium microchaete Mart seeds.

This study aimed to purify and characterize a novel mannose-binding lectin from the seeds of Centrolobium microchaete. Centrolobium microchaete lectin (CML) was purified by affinity chromatography in mannose-Sepharose-4B column. CML agglutinated rabbit erythrocytes and was inhibited by D-mannose, α-methyl-D-mannoside, D-glucose, N-Acetyl-D-glucosamine and sucrose. The lectin was stable at pH 7.0 and 8.0 and temperatures up to 60°C. The monomeric form of CML showed approximately 28kDa, and its native form is probably a homodimer, as determined by gel filtration chromatography. The primary structure of CML was determined by tandem mass spectrometry that showed CML as a protein with two distinct forms (isolectins CML-1 and CML-2) with 246 and 247 residues, respectively. CML-2 possesses one residue of Asn more than CML-1 in C-terminal. The primary structure of CML agrees with the molecular weights found by electrospray ionization mass spectrometry: 27,224 and 27,338Da for CML-1 and CML-2, respectively. CML is a metal-dependent glycoprotein. Moreover, the glycan composition of CML and its structure were predicted.