title: Apoptosis induction of dehydrobruceine B on two kinds of human lung cancer cell lines through mitochondrial-dependent pathway.
abstract: BACKGROUND
  Brucea javanica is an effective traditional medicine listed in Chinese Pharmacopoeia. In China, the seed oil of B. javanica has long been used as commercially available drug for the treatment of tumor in clinic. Dehydrobruceine B (DHB) is a quassinoid isolated from B. javanica.
  
  
  OBJECTIVE
  The aim of the present study is to investigate the apoptotic effects induced by DHB in human lung cancer A549 and NCI-H292 cells. The involvement of a mitochondria-mediated intrinsic pathway in the pro-apoptotic action of DHB was also investigated.
  
  
  METHODS
  Cell viability was determined by MTT assay. Cell cycle and apoptosis were assessed by flow cytometry analysis. Mitochondrial membrane potential (MMP) was examined through JC-1 staining. The protein translocation in cells was examined by immunostaining. The expression levels of proteins which are closely related to mitochondria-mediated apoptosis pathway were measured by immunoblot analysis.
  
  
  RESULTS
  Treatment with DHB decreased cell viability, induced apoptosis and blocked cell cycle at S phase. DHB-induced apoptosis was found to be mediated through mitochondrial intrinsic pathway, evidenced by the loss of MMP, the release of cytochrome c into cytosol, and the cleavage of caspase-9, caspase-3 and poly (ADP-ribose) polymerase (PARP).
  
  
  CONCLUSIONS
  DHB triggers apoptosis in A549 and NCI-H292 cells via mitochondrial pathway, making it a promising candidate as a therapeutic agent for lung carcinoma.
authors.affiliation: Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 Wenhuaxi Road, Jinan 250012, PR China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Pharmacy, Jinan Central Hospital, Shandong University, 105 Jiefang Road, Jinan 250013, PR China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Wen
authors.affiliation: Department of thoracic surgery, Qilu Hospital, Shandong University, 107 Wenhuaxi Road, Jinan 250012, PR China.
authors.forename: Guotao
authors.initials: G
authors.lastname: Yang
authors.affiliation: Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 Wenhuaxi Road, Jinan 250012, PR China.
authors.forename: Zhuqing
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 Wenhuaxi Road, Jinan 250012, PR China.
authors.forename: Tao
authors.initials: T
authors.lastname: Shen
authors.affiliation: Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 Wenhuaxi Road, Jinan 250012, PR China.
authors.forename: Haizhen
authors.initials: H
authors.lastname: Li
authors.affiliation: Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 Wenhuaxi Road, Jinan 250012, PR China. Electronic address: rendom@sdu.edu.cn.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Ren
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002681:China; D045304:Cytochromes c / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D036702:Quassins / Q000737:chemistry*
chemical_list: D036702:Quassins; C000611557:dehydrobruceine B; D045304:Cytochromes c; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9
keywords: Brucea javanica; Dehydrobruceine B; Mitochondrial pathway; Pro-apoptotic action