In Silico and Experimental Studies of Concanavalin A: Insights into Its Antiproliferative Activity and Apoptotic Mechanism

• Published in: Applied biochemistry and biotechnology Vol. 162; no. 1; pp. 134 - 145
• Main Authors: Liu, Zhongyu, Li, Xufeng, Ding, Xianping, Yang, Yi
• Format: Journal Article
• Language: English
• Published: New York New York : Humana Press Inc 01.09.2010; Humana Press Inc; Springer; Springer Nature B.V
• Subjects: Amino Acid Sequence; Animals; Apoptosis; Apoptosis - drug effects; Binding Sites; Biochemistry; Biological and medical sciences; Biotechnology; Carbohydrate Metabolism; caspases; Cell Line; Cell Proliferation; Cell Proliferation - drug effects; Chemistry; Chemistry and Materials Science; Computational Biology; Computational Biology - methods; concanavalin A; Concanavalin A - chemistry; Concanavalin A - metabolism; Concanavalin A - pharmacology; cytochrome c; drug effects; Fundamental and applied biological sciences. Psychology; legumes; membrane potential; metabolism; methods; Mitochondria; Mitochondria - drug effects; molecular dynamics; Molecular Dynamics Simulation; Molecular Sequence Data; Molecular structure; Mortality; pharmacology; Phylogenetics; phylogeny; Phytochemicals; Protein Conformation; Proteins; Phylogenetic analysis; Antiproliferative; Mitochondrial pathway; Molecular structure; Concanavalin A (ConA); Apoptosis; Phylogeny; Concanavalin A; Experimental study; Bioinformatics; Mechanism; Computer aided analysis
• ISSN: 0273-2289; 1559-0291; 1559-0291
• DOI: 10.1007/s12010-009-8694-9

Concanavalin A (ConA), a mannose/glucose-binding legume lectin, has been reported to induce tumor cell death via a mitochondria-mediated autophagic pathway; however, the precise mechanism by which induces cell death remains to be discovered. In this study, we simulated the three-dimensional structure of ConA monomer, its dimer, and tetramer forms and reported its molecular dynamics simulations and phylogenetic analysis. Subsequently, we showed that ConA possessed remarkable antiproliferative effects on HepG2 cells. Further data showed that there was a link among its hemagglutinating, sugar-binding, and antiproliferative activities. In addition, we found that ConA induced apoptosis in HepG2 cells. Then, we demonstrated that the treatment of ConA caused mitochondrial transmembrane potential (MMP) collapse, cytochrome c release, and activation of caspase. In conclusion, we demonstrate that there is a positive correlation between carbohydrate-binding activity and antiproliferative activity of ConA. In addition, we confirm that ConA induces HepG2 cell death through a mitochondrial apoptotic pathway.