title: Emodin induces apoptosis of human osteosarcoma cells via mitochondria- and endoplasmic reticulum stress-related pathways.
abstract: OBJECTIVE
  Emodin showed anti-cancer activity against multiple human malignant tumors by inducing apoptosis. However, the apoptotic inducing effect against human osteosarcoma and related mechanism are still not studied. This study was aimed to investigate them.
  
  
  METHODS
  Emodin was used to incubate human OS cell U2OS cells at serially diluted concentrations. Hoechst staining was used to evaluate apoptosis; flow cytometry was applied to assess the collapse of mitochondrial membrane potential (MMP); intracellular ROS generation was detected by DCFH-DA staining; endoplasmic reticulum stress activation was examined by western blotting.
  
  
  RESULTS
  Cell apoptosis of U2OS cells was induced by emodin incubation in a concentration-dependent manner; MMP collapse and ROS generation were identified at starting concentration of 80 μmol/L of emodin in a concentration-dependent manner. ER stress activation was found at beginning concentration of 40 μmol/L of emodin. The MMP collapse was inhibited while the ER stress was not inhibited by NAC administration.
  
  
  CONCLUSIONS
  Emodin induces death of human osteosarcoma cells by initiating ROS-dependent mitochondria-induced and ROS-independent ER stress-induced apoptosis.
authors.affiliation: Department of Orthopedics, Lishui Central Hosptial Lishui, Zhejiang, China.
authors.forename: Jinhe
authors.initials: J
authors.lastname: Ying
authors.affiliation: Department of Orthopedics, Lishui Central Hosptial Lishui, Zhejiang, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Orthopedics, Lishui Central Hosptial Lishui, Zhejiang, China.
authors.forename: Dhua
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Orthopedics, Lishui Central Hosptial Lishui, Zhejiang, China.
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Wu
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001859:Bone Neoplasms / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004642:Emodin / Q000494:pharmacology*; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D012516:Osteosarcoma / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D047428:Protein Kinase Inhibitors; D017382:Reactive Oxygen Species; D053148:Caspase 3; D004642:Emodin
keywords: Osteosarcoma; apoptosis; emodin; endoplasmic reticulum stress; mitochondria; reactive oxygen species