Effect of quercetin on apoptosis of PANC-1 cells.
10.4174/jkss.2013.85.6.249
- Author:
Joo Hyun LEE
1
;
Han Beom LEE
;
Gum O JUNG
;
Jung Taek OH
;
Dong Eun PARK
;
Kwon Mook CHAE
Author Information
1. Division of Hepatobiliary Surgery, Department of Surgery, Wonkwang University School of Medicine & Hospital, Iksan, Korea. chaekm@wonkwang.ac.kr
- Publication Type:Original Article
- Keywords:
Quercetin;
Drug therapy;
Apoptosis;
Pancreatic neoplasms
- MeSH:
Apoptosis*;
Benzimidazoles;
Blotting, Western;
Carbocyanines;
Cell Cycle;
Cell Survival;
Chromatin;
Cisplatin;
Deoxycytidine;
DNA Fragmentation;
Doxorubicin;
Drug Therapy;
Flow Cytometry;
Fluorescence;
Fluorouracil;
Humans;
Membrane Potential, Mitochondrial;
Pancreatic Neoplasms;
Quercetin*;
Reactive Oxygen Species;
Reticulum;
Rhodamine 123
- From:Journal of the Korean Surgical Society
2013;85(6):249-260
- CountryRepublic of Korea
- Language:English
-
Abstract:
PURPOSE: 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 microg/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 Ca2+ 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. CONCLUSION: These data suggest that quercetin may be an important modulator of chemosensitivity of cancer cells against anticancer chemotherapeutic agents.
