title: Anti-proliferation effects of isorhamnetin on lung cancer cells in vitro and in vivo.
abstract: BACKGROUND
  Isorhamnetin (Iso), a novel and essential monomer derived from total flavones of Hippophae rhamnoides that has long been used as a traditional Chinese medicine for angina pectoris and acute myocardial infarction, has also shown a spectrum of antitumor activity. However, little is known about the mechanisms of action Iso on cancer cells.
  
  
  OBJECTIVE
  To investigate the effects of Iso on A549 lung cancer cells and underlying mechanisms.
  
  
  METHODS
  A549 cells were treated with 10~320 μg/ml Iso. Their morphological and cellular characteristics were assessed by light and electronic microscopy. Growth inhibition was analyzed by MTT, clonogenic and growth curve assays. Apoptotic characteristics of cells were determined by flow cytometry (FCM), DNA fragmentation, single cell gel electrophoresis (comet) assay, immunocytochemistry and terminal deoxynucleotidyl transferase nick end labeling (TUNEL) . Tumor models were setup by transplanting Lewis lung carcinoma cells into C57BL/6 mice, and the weights and sizes of tumors were measured.
  
  
  RESULTS
  Iso markedly inhibited the growth of A549 cells with induction of apoptotic changes. Iso at 20 μg/ml, could induce A549 cell apoptosis, up-regulate the expression of apoptosis genes Bax, Caspase-3 and P53, and down-regulate the expression of Bcl-2, cyclinD1 and PCNA protein. The tumors in tumor-bearing mice treated with Iso were significantly smaller than in the control group. The results of apoptosis-related genes, PCNA, cyclinD1 and other protein expression levels of transplanted Lewis cells were the same as those of A549 cells in vitro.
  
  
  CONCLUSIONS
  Iso, a natural single compound isolated from total flavones, has antiproliferative activity against lung cancer in vitro and in vivo. Its mechanisms of action may involve apoptosis of cells induced by down-regulation of oncogenes and up-regulation of apoptotic genes.
authors: School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, China E-mail : zhuling529@163.com.
authors: Qiong
authors: Q
authors: Li
authors: Fu-Qiang
authors: FQ
authors: Ren
authors: Chun-Lei
authors: CL
authors: Yang
authors: Li-Ming
authors: LM
authors: Zhou
authors: Yan-You
authors: YY
authors: Liu
authors: Jing
authors: J
authors: Xiao
authors: Ling
authors: L
authors: Zhu
authors: Zhen-Grong
authors: ZG
authors: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D018827:Carcinoma, Lewis Lung / Q000178:diet therapy / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D019938:Cyclin D1 / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011794:Quercetin / Q000031:analogs & derivatives* / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D018809:Proliferating Cell Nuclear Antigen; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C047368:3-methylquercetin; D019938:Cyclin D1; D011794:Quercetin; D053148:Caspase 3