title: Fisetin Reduces Cell Viability Through Up-Regulation of Phosphorylation of ERK1/2 in Cholangiocarcinoma Cells.
abstract: Cholangiocarcinoma (CCA) is a malignancy with poor prognosis and limited therapeutic options. Effective prevention and treatment of CCA require developing novel anticancer agents and improved therapeutic regimens. As natural products are concidered a rich source of potential anticancer agents, we investigated the anticancer effect of fisetin in combination with gemcitabine.
  
  
  
  Cytotoxic effect of fisetin and gemcitabine on a human CCA cell line SNU-308 was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and apoptosis assay using propidium iodine and annexin V. Molecular mechanisms of fisetin action in CCA were investigated by western blotting.
  
  
  
  Fisetin was found to inhibit survival of CCA cells, through strongly phosphorylating ERK. It also induced cellular apoptosis additively in combination with gemcitabine. Expression of cellular proliferative markers, such as phospho-p65 and myelocytomatosis (MYC), were reduced by fisetin.
  
  
  
  These results suggest fisetin in combination with gemcitabine as a candidate for use in improved anticancer regimens.
authors: Department of Convergence Medicine & Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors: Nayoung
authors: N
authors: Kim
authors: Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea gidoctor@snuh.org.
authors: Sang Hyub
authors: SH
authors: Lee
authors: Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors: Jun Hyuk
authors: JH
authors: Son
authors: Department of Internal Medicine, Gyeongsang National University College of Medicine, Gyeongsang National University Changwon Hospital, Changwon, Republic of Korea.
authors: Jae Min
authors: JM
authors: Lee
authors: Department of Convergence Medicine & Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors: Min-Jung
authors: MJ
authors: Kang
authors: Department of Convergence Medicine & Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors: Bo Hye
authors: BH
authors: Kim
authors: Department of Convergence Medicine & Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
authors: Jung-Su
authors: JS
authors: Lee
authors: Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors: Ji Kon
authors: JK
authors: Ryu
authors: Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors: Yong-Tae
authors: YT
authors: Kim
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects*; D018281:Cholangiocarcinoma / Q000473:pathology*; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology*; D044948:Flavonols; D006801:Humans; D020935:MAP Kinase Signaling System; D010766:Phosphorylation; D015854:Up-Regulation / Q000187:drug effects*; D000093542:Gemcitabine
chemical_list: D005419:Flavonoids; D044948:Flavonols; D003841:Deoxycytidine; C017875:fisetin; D000093542:Gemcitabine
keywords: Fisetin; anticancer; cholangiocarcinoma; combinatory treatment; gemcitabine