title: Leonurine hydrochloride induces apoptosis of H292 lung cancer cell by a mitochondria-dependent pathway.
abstract: BACKGROUND
  Leonurine hydrochloride (LH), a major alkaloid compound extracted from Leonurus japonicas Houtt. (Labiatae), is considered to have antitumor roles.
  
  
  OBJECTIVE
  This study investigated its effects on human non-small cell lung cancer (NSCLC) H292 cells and illustrated the possible mechanism involved.
  
  
  METHODS
  After treatment with different concentrations of LH (0, 10, 25, and 50 μmol/L) for 6, 12, 24, 48, and 72 h, the cell viability was assessed by the MTT assay. After exposed to different doses of LH for 24 h, cell-cycle distribution, cell apoptosis, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) were monitored by flow cytometry. RT-PCR and western blot were used to detect the expression of apoptosis-related genes.
  
  
  RESULTS
  LH significantly inhibited the proliferation of H292 cells in a time- and dose-dependent manner, and induced G0/G1 cell-cycle arrest. Coincidentally, LH treatment at a dose of 10, 25, and 50 μmol/L for 24 h increased apoptotic ratio from 4.9 ± 0.43% to 11.5 ± 1.12%, 19.3 ± 1.16%, and 61.3 ± 6.69%, respectively. The inhibition effect of LH on H292 cells was associated with the loss of MMP and the generation of ROS. The phosphorylation level of p38 was increased and Akt phosphorylation was reduced by LH treatment. Furthermore, LH treatment increased the expression levels of caspase-3, caspase-9 and Bax/Bcl-2.
  
  
  CONCLUSIONS
  LH inhibits the proliferation and induces the apoptosis of H292 cells in a mitochondria-dependent pathway, and the specific mechanism need to be further explored.
authors: Department of Clinical Center for Lung Cancer, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao-Tong University , Shanghai , China .
authors: Feng
authors: F
authors: Mao
authors: Liang
authors: L
authors: Zhang
authors: Ming-Hui
authors: MH
authors: Cai
authors: Hong
authors: H
authors: Guo
authors: Hai-Hua
authors: HH
authors: Yuan
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D019686:Lamiaceae; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D010936:Plant Extracts; C013587:leonurine; D005707:Gallic Acid
keywords: MMP; Mitochondria; NSCLC; ROS