title: Grandinin down-regulates phosphorylation of epidermal growth factor receptor.
abstract: OBJECTIVE
  Grandinin (C(46)H(34)O(30)) is a compound found in Melaleuca quinquenervia leaves and in oaks. This study is to determine effects of grandinin on malignant lung cells and the related molecular mechanisms.
  
  
  METHODS
  Malignant cells were treated with grandinin with various concentrations. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrozolium bromide (MTT) assays and apoptosis assays were performed to determine effects of grandinin on cell viability and apoptosis. Western blotting and real time-PCR were used to determine if grandinin affects levels of phosphorylated EGFR (p-EGFR) and phosphorylated AKT (p-AKT), as well as their mRNA transcript levels.
  
  
  RESULTS
  It was found that grandinin treatments reduce viability of malignant lung cells and induces apoptosis. When treated with grandinin (16 μM), the apoptosis of the three lung cancer cell lines MS-1, A549, and LK-2 were increased by 8-9 folds, in comparison with the cells treated with DMSO only (the control condition). Furthermore, grandinin treatments lead to down-regulation of levels of p-EGFR and p-AKT in three malignant lung cell lines. However, grandinin does not affect mRNA levels of EGFR and AKT.
  
  
  CONCLUSIONS
  These experimental results indicated grandinin significantly reduce malignant cell viability and effectively induces apoptosis of malignant lung cells by mediating phosphorylation down-regulation of cellular signaling proteins EGFR and AKT. It is suggested that grandinin treatments might be an effective therapeutic strategy of lung malignancies upon further studies in the future.
authors.affiliation: The Affiliated Hospital of Qingdao University Qingdao 266021, Shandong Province, China.
authors.forename: Zhuling
authors.initials: Z
authors.lastname: Qu
authors.affiliation: The Affiliated Hospital of Qingdao University Qingdao 266021, Shandong Province, China.
authors.forename: Aiqin
authors.initials: A
authors.lastname: Song
authors.affiliation: The Affiliated Hospital of Qingdao University Qingdao 266021, Shandong Province, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Feng
authors.affiliation: The Affiliated Hospital of Qingdao University Qingdao 266021, Shandong Province, China.
authors.forename: Ruyang
authors.initials: R
authors.lastname: Teng
authors.affiliation: The Affiliated Hospital of Qingdao University Qingdao 266021, Shandong Province, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Gao
authors.affiliation: The Affiliated Hospital of Qingdao University Qingdao 266021, Shandong Province, China.
authors.forename: Xuanlong
authors.initials: X
authors.lastname: Yi
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D066246:ErbB Receptors / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006027:Glycosides / Q000494:pharmacology*; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology*; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D006027:Glycosides; D006576:Heterocyclic Compounds, 4 or More Rings; D012333:RNA, Messenger; C479598:grandinin; C512478:EGFR protein, human; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt
keywords: Grandinin; down-regulates phosphorylation; epidermal growth factor receptor; phosphorylation