Antiproliferative activity and apoptosis-inducing mechanism of Concanavalin A on human melanoma A375 cells.
The objective of this study was to investigate the antiproliferative activity and apoptosis-inducing mechanism of Concanavalin A (ConA) on human melanoma A375 cells. We firstly simulated the three-dimensional structure of ConA. Subsequently, we found that ConA possessed remarkable antiproliferative effect on A375 cells. Further experimental data indicated that there was a link between its hemagglutinating activity, mannose-binding activity and antiproliferative activity. In addition, we showed that ConA induced A375 cell apoptosis in a caspase-dependent manner. Then, we demonstrated that the treatment of ConA caused mitochondrial transmembrane potential (MMP) collapse, cytochrome c release and caspase activation. In conclusion, we report for the first time that there may be a close correlation between carbohydrate-binding activity of ConA and its antiproliferative activity. Also, we demonstrate firstly that ConA induces A375 cell death in a caspase-dependent manner as well as through a mitochondrial apoptotic pathway.
Liu
Bo
B
College of Life Sciences, State Key Laboratory of Oral Diseases, Sichuan University, Chengdu, China.
Li
Chun-yang
CY
Bian
He-jiao
HJ
Min
Ming-wei
MW
Chen
Long-fei
LF
Bao
Jin-ku
JK
D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D003198:Computer Simulation; D003208:Concanavalin A / Q000737:chemistry / Q000494:pharmacology*; D006384:Hemagglutination / Q000187:drug effects; D006801:Humans; D008358:Mannose / Q000494:pharmacology; D008545:Melanoma; D008564:Membrane Potentials / Q000187:drug effects; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000502:physiology; D008958:Models, Molecular; D008968:Molecular Conformation
D003208:Concanavalin A; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D008358:Mannose