title: In silico and experimental studies of concanavalin A: insights into its antiproliferative activity and apoptotic mechanism.
abstract: 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.
authors: College of Life Sciences, Sichuan University, Chengdu 610064, China. zhongyujohn@gmail.com
authors: Zhongyu
authors: Z
authors: Liu
authors: Xufeng
authors: X
authors: Li
authors: Xianping
authors: X
authors: Ding
authors: Yi
authors: Y
authors: Yang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001665:Binding Sites; D050260:Carbohydrate Metabolism; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D019295:Computational Biology / Q000379:methods*; D003208:Concanavalin A / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D011487:Protein Conformation
chemical_list: D003208:Concanavalin A