title: Dehydroabietic Acid Derivative QC4 Induces Gastric Cancer Cell Death via Oncosis and Apoptosis.
abstract: OBJECTIVE
  QC4 is the derivative of rosin's main components dehydroabietic acid (DHA). We investigated the cytotoxic effect of QC4 on gastric cancer cells and revealed the mechanisms beneath the induction of cell death.
  
  
  METHODS
  The cytotoxic effect of QC4 on gastric cancer cells was evaluated by CCK-8 assay and flow cytometry. The underlying mechanisms were tested by administration of cell death related inhibitors and detection of apoptotic and oncosis related proteins. Cytomembrane integrity and organelles damage were confirmed by lactate dehydrogenase (LDH) leakage assay, mitochondrial function test, and cytosolic free Ca(2+) concentration detection.
  
  
  RESULTS
  QC4 inhibited cell proliferation dose- and time-dependently and destroyed cell membrane integrity, activated calpain-1 autolysis, and induced apoptotic protein cleavage in gastric cancer cells. The detection of decreased ATP and mitochondrial membrane potential, ROS accumulation, and cytosolic free Ca(2+) elevation confirmed organelles damage in QC4-treated gastric cancer cells.
  
  
  CONCLUSIONS
  DHA derivative QC4 induced the damage of cytomembrane and organelles which finally lead to oncosis and apoptosis in gastric cancer cells. Therefore, as a derivative of plant derived small molecule DHA, QC4 might become a promising agent in gastric cancer therapy.
authors.affiliation: Department of Hepatobiliary Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu 210008, China.
authors.forename: Dongjun
authors.initials: D
authors.lastname: Luo
authors.affiliation: Department of General Surgery, The Second Clinical Medical School of Yangzhou University, Jiangsu 225000, China; Department of General Surgery, Frist People's Hospital of Yangzhou, Yangzhou, Jiangsu 225000, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Ni
authors.affiliation: Department of General Surgery, The Second Clinical Medical School of Yangzhou University, Jiangsu 225000, China; Department of General Surgery, Frist People's Hospital of Yangzhou, Yangzhou, Jiangsu 225000, China.
authors.forename: Anlai
authors.initials: A
authors.lastname: Ji
authors.affiliation: College of Chemical Engineering, Nanjing Forestry University, Nanjing, Jiangsu 210037, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Gu
authors.affiliation: Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing, Jiangsu 210093, China.
authors.forename: Junhua
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Hepatobiliary Surgery, Nanjing Drum Tower Hospital Clinical 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: Chunping
authors.identifier: 0000-0002-5191-4000
authors.initials: C
authors.lastname: Jiang
mesh_terms: D045784:Abietanes / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D006801:Humans; D013274:Stomach Neoplasms
chemical_list: D045784:Abietanes; D000970:Antineoplastic Agents; C013913:dehydroabietic acid