title: Total flavonoid aglycones extract in Radix scutellariae inhibits lung carcinoma and lung metastasis by affecting cell cycle and DNA synthesis.
abstract: BACKGROUND
  Radix Scutellariae (Scutellaria baicalensis Georgi, RS), a traditional herbal medicine commonly used to treat inflammation, hypertension, cardiovascular disease, bacterial and viral infections, is reported to treat lung cancer by supplements of modern medicine. The total flavonoid aglycones extract (TFAE) from RS is the most important composition for the pharmacodynamic effects. The present study was designed to evaluate the anti-lung tumor effect of TFAE on A549 cells and A549 cell nude mice xenografts. The aim of the study is to investigate the effect and mechanism of TFAE treating non-small cell lung cancer both in vitro and in vivo.
  
  
  METHODS
  The anti-tumor activity of TFAE in vitro was investigated using the MTT assay. The changes of cell invasion and migration were detected by Transwell assay and tube formation experiments were used to detect the anti-angiogenic effect. The anti-tumor effects of TFAE in vivo were evaluated in A549 cell nude mice xenografts. The mechanism of TFAE was detected by flow cytometry technology, western blot assay and immuno-histochemistry assay.
  
  
  RESULTS
  In vitro, TFAE inhibited the proliferation, invasion and migration of A549 cells in a dose- and time-dependent manner. In vivo, TFAE by oral administration at 100mg/kg for 30 days decreased the tumor volume and tumor weight in A549 cell xenograft by 25.5% with no statistical significance (P<0.05) compared to the cis-platinum positive control group (30.0%). The cell cycle and DNA synthesis experiment illustrated that TFAE could induce A549 cell cycle to arreste in S phase and DNA synthesis in A549 cells be inhibited, while TFAE had no influence on apoptosis of A549 cells. Western Blot assay demonstrated that the treatment of TFAE could make Cyclin D1 decrease and p53 increase both in vitro and in vivo.
  
  
  CONCLUSIONS
  TFAE displayed the inhibition effects of non-small cell lung cancer both in vitro and in vivo and the underlying mechanism might be related to the increased p53 protein expression and decreased Cyclin D1 expression, leading to cell cycle arrested in S phase and the decrease of DNA synthesis.
authors.affiliation: Center for Traditional Chinese Medicine and Systems Biology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: North China University of Science and Technology, TangShan 063000, HeBei, China.
authors.forename: Hui-Juan
authors.initials: HJ
authors.lastname: Cao
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China; Unimicro (Shanghai) Technologics Co., Ltd., Shanghai 201203, China.
authors.forename: Shu-Jun
authors.initials: SJ
authors.lastname: Sun
authors.affiliation: Department of Chemical Biology, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
authors.forename: Jian-Ye
authors.initials: JY
authors.lastname: Dai
authors.affiliation: Center for Traditional Chinese Medicine and Systems Biology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Jun-Wei
authors.initials: JW
authors.lastname: Fang
authors.affiliation: Center for Traditional Chinese Medicine and Systems Biology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Qian-Hua
authors.initials: QH
authors.lastname: Li
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Yan
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China. Electronic address: wwmao@sjtu.edu.cn.
authors.forename: Wen-Wei
authors.initials: WW
authors.lastname: Mao
authors.affiliation: Center for Traditional Chinese Medicine and Systems Biology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: dryyz@sina.com.
authors.forename: Yong-Yu
authors.initials: YY
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002453:Cell Cycle; D045744:Cell Line, Tumor; D004261:DNA Replication; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D010936:Plant Extracts / Q000494:pharmacology*; D031363:Scutellaria / Q000737:chemistry*
chemical_list: D005419:Flavonoids; D010936:Plant Extracts
keywords: Cell cycle; DNA synthesis; Lung carcinoma; Total flavonoid aglycones extract