title: Dehydroabietic acid derivative QC2 induces oncosis in hepatocellular carcinoma cells.
abstract: OBJECTIVE
  Rosin, the traditional Chinese medicine, is reported to be able to inhibit skin cancer cell lines. In this report, we investigate the inhibitory effect against HCC cells of QC2, the derivative of rosin's main components dehydroabietic acid.
  
  
  METHODS
  MTT assay was used to determine the cytotoxicity of QC2. Morphological changes were observed by time-lapse microscopy and transmission electron microscopy and the cytoskeleton changes were observed by laser-scanning confocal microscopy. Cytomembrane integrity and organelles damage were confirmed by detection of the reactive oxygen (ROS), lactate dehydrogenase (LDH), and mitochondrial membrane potential (Δψm). The underlying mechanism was manifested by Western blotting. The oncotic cell death was further confirmed by detection of oncosis related protein calpain.
  
  
  RESULTS
  Swelling cell type and destroyed cytoskeleton were observed in QC2-treated HCC cells. Organelle damage was visualized by transmission electron microscopy. The detection of ROS accumulation, increased LDH release, and decreased ATP and Δψm confirmed the cell death. The oncotic related protein calpain was found to increase time-dependently in QC2-treated HCC cells, while its inhibitor PD150606 attenuated the cytotoxicity.
  
  
  CONCLUSIONS
  Dehydroabietic acid derivative QC2 activated oncosis related protein calpain to induce the damage of cytomembrane and organelles which finally lead to oncosis in HCC cells.
authors.affiliation: Department of Hepatobiliary Surgery, Drum Tower Clinical Medical College of Nanjing Medical University, Nanjing, Jiangsu 210008, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Hepatobiliary Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, China.
authors.forename: Chunping
authors.initials: C
authors.lastname: Jiang
authors.affiliation: Department of Hepatobiliary Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, China ; School of Medicine, Nanjing University, Nanjing, Jiangsu 210093, China.
authors.forename: Zhongxia
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Hepatobiliary Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, China ; School of Medicine, Nanjing University, Nanjing, Jiangsu 210093, China.
authors.forename: Weibo
authors.initials: W
authors.lastname: Chen
authors.affiliation: College of Chemical Engineering, Nanjing Forestry University, Nanjing, Jiangsu 210037, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Gu
authors.affiliation: Department of Hepatobiliary Surgery, Drum Tower Clinical Medical College of Nanjing Medical University, Nanjing, Jiangsu 210008, China ; Department of Hepatobiliary Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, China.
authors.forename: Yitao
authors.initials: Y
authors.lastname: Ding
mesh_terms: D045784:Abietanes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000172:deficiency; D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D002154:Calpain / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology* / Q000648:ultrastructure; D053148:Caspase 3 / Q000378:metabolism; D061945:Caspase Inhibitors / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003599:Cytoskeleton / Q000187:drug effects / Q000648:ultrastructure; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology* / Q000648:ultrastructure; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D045784:Abietanes; D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; D007093:Imidazoles; D007211:Indoles; D017382:Reactive Oxygen Species; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C507699:necrostatin-1; C013913:dehydroabietic acid; D000255:Adenosine Triphosphate; D002154:Calpain; D053148:Caspase 3
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