title: Effect of quercetin on apoptosis of PANC-1 cells.
abstract: OBJECTIVE
  To investigate the chemotherapeutic effect of quercetin against cancer cells, signaling pathway of apoptosis was explored in human pancreatic cells.
  
  
  METHODS
  Various anticancer drugs including adriamycin, cisplatin, 5-fluorouracil (5-FU) and gemcitabine were used. Cell viability was measured by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphe-nyltetra zolium bromide assay. Apoptosis was determined by 4'-6-diamidino-2-phenylindole nuclei staining and flow cytometry in PANC-1 cells treated with 50 µg/mL quercetin for 24 hours. Expression of endoplas mic reticulum (ER) stress mediators including, Grp78/Bip, p-PERK, PERK, ATF4, ATF6 and GADD153/CHOP proteins were measured by Western blot analysis. Mitochondrial membrane potential was measured by fluorescence staining with JC-1, rhodamine 123. Quercetin induced the apoptosis of PANC-1, which was characterized as nucleic acid and genomic DNA fragmentation, chromatin condensation, and sub-G0/G1 fraction of cell cycle increase. But not adriamycin, cisplatin, gemcitabine, and 5-FU. PANC-1 cells were markedly sensitive to quercetin.
  
  
  RESULTS
  Treatment with quercetin resulted in the increased accumulation of intracellular Ca(2+) ion. Treatment with quercetin also increased the expression of Grp78/Bip and GADD153/CHOP protein and induced mitochondrial dysfunction. Quercetin exerted cytotoxicity against human pancreatic cancer cells via ER stress-mediated apoptotic signaling including reactive oxygen species production and mitochondrial dysfunction.
  
  
  CONCLUSIONS
  These data suggest that quercetin may be an important modulator of chemosensitivity of cancer cells against anticancer chemotherapeutic agents.
authors.affiliation: Division of Hepatobiliary Surgery, Department of Surgery, Wonkwang University School of Medicine & Hospital, Iksan, Korea.
authors.forename: Joo Hyun
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Division of Hepatobiliary Surgery, Department of Surgery, Wonkwang University School of Medicine & Hospital, Iksan, Korea.
authors.forename: Han-Beom
authors.initials: HB
authors.lastname: Lee
authors.affiliation: Division of Hepatobiliary Surgery, Department of Surgery, Wonkwang University School of Medicine & Hospital, Iksan, Korea.
authors.forename: Gum O
authors.initials: GO
authors.lastname: Jung
authors.affiliation: Division of Hepatobiliary Surgery, Department of Surgery, Wonkwang University School of Medicine & Hospital, Iksan, Korea.
authors.forename: Jung Taek
authors.initials: JT
authors.lastname: Oh
authors.affiliation: Division of Hepatobiliary Surgery, Department of Surgery, Wonkwang University School of Medicine & Hospital, Iksan, Korea.
authors.forename: Dong Eun
authors.initials: DE
authors.lastname: Park
authors.affiliation: Division of Hepatobiliary Surgery, Department of Surgery, Wonkwang University School of Medicine & Hospital, Iksan, Korea.
authors.forename: Kwon Mook
authors.initials: KM
authors.lastname: Chae
keywords: Apoptosis; Drug therapy; Pancreatic neoplasms; Quercetin