Induction of autophagy by concanavalin A and its application in anti-tumor therapy.
Concanavalin A (Con A), a lectin from Jack bean seeds that, once bound to the mannose moiety on the cell membrane glycoprotein, is internalized preferentially to the mitochondria. A BNIP3-mediated mitochondria autophagy is then induced, and causes the tumor cells to undergo autophagic cell death. Con A is also a T cell mitogen that can induce autoimmune hepatitis in mice. Because of the dual properties (autophagic cytotoxicity and immunomodulation) via the specific mannose binding, Con A can exert a potent anti-hepatoma therapeutic effect by inhibiting tumor nodule formation in the liver and prolonging the survival of the tumor-bearing mice. The anti-tumor effect is primarily mediated by activated CD8(+) T cells, and will also establish a tumor antigen-specific immune memory during the hepatic inflammation. This finding provides a novel mechanism in which Con A can be used as an anti-hepatoma agent, and also gives support for the search for natural lectins as anti-cancer compounds.
Lei
Huan-Yao
HY
Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan. hylei@mail.ncku.edu.tw
Chang
Chih-Peng
CP
D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D003208:Concanavalin A / Q000494:pharmacology* / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000188:drug therapy*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008934:Mitogens / Q000494:pharmacology* / Q000627:therapeutic use*
D008934:Mitogens; D003208:Concanavalin A