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KMID : 0371320130850060249
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Journal of the Korean Surgical Society
2013 Volume.85 No. 6 p.249 ~ p.260
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Effect of quercetin on apoptosis of PANC-1 cells
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Lee Joo-Hyun
Lee Han-Beom
Jung Gum-O
Oh Jung-Taek
Park Dong-Eun
Chae Kwon-Mook
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Abstract
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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 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 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.
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KEYWORD
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Quercetin, Drug therapy, Apoptosis, Pancreatic neoplasms
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