4.6 Article

Antiproliferative activity and apoptosis-inducing mechanism of Concanavalin A on human melanoma A375 cells

Journal

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
Volume 482, Issue 1-2, Pages 1-6

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.abb.2008.12.003

Keywords

Concanavalin A (ConA); Molecular modeling; Antiproliferative; Apoptosis; Caspase; Mitochondria

Funding

  1. National Natural Science Foundation of China [30270331, 30670469]
  2. State Key Laboratory of Oral Diseases (Sichuan University).

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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. (C) 2008 Elsevier Inc. All rights reserved.

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