Concanavalin A induces autophagy in hepatoma cells and has a therapeutic effect in a murine in situ hepatoma model.
Concanavalin A (ConA), a lectin with mannose specificity that can induce acute hepatic inflammation, was tested for its therapeutic effect against hepatoma. ConA is cytotoxic or inhibitory to hepatoma cells, which is mediated by the autophagic pathway through mitochondria. Once it was bound to cell membrane glycoproteins, the ConA was internalized and preferentially localized onto the mitochondria. The mitochondria membrane permeability changed, and an autophagic pathway including LC3-II generation, double-layer vesicle, BNIP3 induction, and acidic vesicular organelle formation was induced. Either 3-MA or siRNA for BNIP3 and LC3, but neither beclin-1 nor ATG 5, partially inhibited the ConA-induced cell death. In addition to the autophagy induction, ConA is known to be a T cell mitogen. Using an in situ hepatoma model, ConA can exert an anti-hepatoma therapeutic effect, inhibiting tumor nodule formation in the liver and prolonging survival.


CONCLUSIONS
ConA can be considered as an anti-hepatoma agent therapeutically because of its autophagic induction and immunomodulating activity. This dual function of ConA provides a novel mechanism for the biological effect of lectin.
Chang
Chih-Peng
CP
Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Republic of China.
Yang
Ming-Cheng
MC
Liu
Hsiao-Sheng
HS
Lin
Yee-Shin
YS
Lei
Huan-Yao
HY
D000818:Animals; D051017:Apoptosis Regulatory Proteins; D001343:Autophagy / Q000187:drug effects*; D000071187:Autophagy-Related Protein 5; D000071186:Beclin-1; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003208:Concanavalin A / Q000494:pharmacology* / Q000627:therapeutic use*; D004195:Disease Models, Animal; D037102:Lectins / Q000494:pharmacology / Q000627:therapeutic use; D008113:Liver Neoplasms / Q000188:drug therapy*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D008869:Microtubule-Associated Proteins / Q000235:genetics; D051336:Mitochondrial Membranes / Q000187:drug effects; D024101:Mitochondrial Proteins / Q000235:genetics; D008934:Mitogens / Q000494:pharmacology* / Q000627:therapeutic use*; D011506:Proteins / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology
D051017:Apoptosis Regulatory Proteins; C495773:Atg5 protein, mouse; D000071187:Autophagy-Related Protein 5; C508686:BNip3 protein, mouse; D000071186:Beclin-1; C115010:Becn1 protein, mouse; D037102:Lectins; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; D008934:Mitogens; D011506:Proteins; D034741:RNA, Small Interfering; D003208:Concanavalin A