title: Casticin induces apoptosis and G0/G1 cell cycle arrest in gallbladder cancer cells.
abstract: BACKGROUND
  Casticin, the flavonoid extracted fromVitex rotundifoliaL, exerts various biological effects, including anti-inflammatory and anti-cancer activity. The aim of this study is to investigate the effects and mechanisms of casticin in human gallbladder cancer cells.
  
  
  METHODS
  Human NOZ and SGC996 cells were used to perform the experiments. CCK-8 assay and colony formation assay were performed to evaluate cell viability. Cell cycle analyses and annexin V/PI staining assay for apoptosis were measured using flow cytometry. Western blot analysis was used to evaluate the changes in protein expression, and the effect of casticin treatment in vivo was experimented with xenografted tumors.
  
  
  RESULTS
  In this study, we found that casticin significantly inhibited gallbladder cancer cell proliferation in a dose- and time-dependent manner. Casticin also induced G0/G1 arrest and mitochondrial-related apoptosis by upregulating Bax, cleaved caspase-3, cleaved caspase-9 and cleaved poly ADP-ribose polymerase expression, and by downregulating Bcl-2 expression. Moreover, casticin induced cycle arrest and apoptosis by upregulating p27 and downregulating cyclinD1/cyclin-dependent kinase4 and phosphorylated protein kinase B. In vivo, casticin inhibited tumor growth.
  
  
  CONCLUSIONS
  Casticin induces G0/G1 arrest and apoptosis in gallbladder cancer, suggesting that casticin might represent a novel and effective agent against gallbladder cancer.
authors.affiliation: Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.|Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Xiao-Ling
authors.initials: XL
authors.lastname: Song
authors.affiliation: Department of Cardio-Thoracic Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Yun-Jiao
authors.initials: YJ
authors.lastname: Zhang
authors.affiliation: Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Xue-Feng
authors.initials: XF
authors.lastname: Wang
authors.affiliation: Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Wen-Jie
authors.initials: WJ
authors.lastname: Zhang
authors.affiliation: Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.|Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.|Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Fei
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.|Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Yi-Jian
authors.initials: YJ
authors.lastname: Zhang
authors.affiliation: Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Lu
authors.affiliation: Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Jia-Wei
authors.initials: JW
authors.lastname: Mei
authors.affiliation: Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.|Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Yun-Ping
authors.initials: YP
authors.lastname: Hu
authors.affiliation: Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.|Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Huai-Feng
authors.initials: HF
authors.lastname: Li
authors.affiliation: Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.|Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Ye
authors.affiliation: Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.|Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Ying-Bin
authors.initials: YB
authors.lastname: Liu
authors.affiliation: Department of General Surgery and Laboratory of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.|Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Gu
keywords: Akt signaling pathway; Apoptosis; Casticin; G0/G1 arrest; Gallbladder cancer