title: Autophagy Inhibits Apoptosis Induced by agrocybe aegerita Lectin in Hepatocellular Carcinoma.
abstract: BACKGROUND
  Lectins are carbohydrate-binding proteins that exhibit remarkable antitumor activities by inducing apoptotic or autophagic cell death. However, the relationship between apoptosis and autophagy induced by lectins has rarely been reported. Agrocybe aegerita lectin (AAL), a lectin isolated from the fungus Agrocybe aegerita, exerts antitumor activity through apoptosis.
  
  
  OBJECTIVE
  To study the relationship between the autophagy and apoptosis induced by AAL in hepatocellular carcinoma (HCC) cells, and then to promote the antitumor effect of AAL.
  
  
  METHODS
  AAL was evaluateted using the CCK-8 kit and the trypan blue assay. Cell autophagy was studied using western blotting, acridine orange straining, transmission electron microscopy, and transient transfection of pEGFPLC3 plasmids. We also evaluated AAL-induced autophagy in Caenorhabditis elegans. Apoptosis was studied using flow cytometry. We also identified the antitumor effects of co-treatment of AAL with chloroquine (CQ) in vitro and in vivo.
  
  
  RESULTS
  AAL-treated cell lines showed accumulation of microtubule-associated protein light chain 3 II (LC3-II), formation of EGFP-LC3 puncta and acidic autophagic vacuoles (AVOs), and the induction of autophagosomes. Inhibition of autophagy could enhance apoptosis induced by AAL in HCC cells. Furthermore, co-therapy (AAL and chloroquine) promote antitumor effect of AAL in a murine in situ HCC model.
  
  
  CONCLUSIONS
  Our findings suggest that inhibition of autophagy exerts a synergistic effect on the antitumor activity of AAL and may be a helpful strategy for reducing the dosage of lectin used in antitumor therapy. The autophagy inhibitor may be a synergist of certain antitumor drugs that can induce both apoptosis and autophagy.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Guojun
authors.initials: G
authors.lastname: Yu
authors.forename: Wenhui
authors.initials: W
authors.lastname: Yu
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Ye
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Jin
authors.forename: Alok
authors.initials: A
authors.lastname: Shrestha
authors.forename: Qing
authors.initials: Q
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Virology, College of Life Science, Wuhan University, Wuhan, 430072, Hubei Province, P.R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Sun
mesh_terms: D055362:Agrocybe / Q000737:chemistry*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D017173:Caenorhabditis elegans / Q000166:cytology / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D006801:Humans; D037102:Lectins / Q000737:chemistry / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D037102:Lectins