Effect of quercetin on apoptosis of PANC-1 cells

Abstract

PurposeTo investigate the chemotherapeutic effect of quercetin against cancer cells, signaling pathway of apoptosis was explored in human pancreatic cells.MethodsVarious 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.ResultsTreatment 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.ConclusionThese data suggest that quercetin may be an important modulator of chemosensitivity of cancer cells against anticancer chemotherapeutic agents.

Quercetin induced cell apoptosis and altered gene expression in AGS human gastric cancer cells

“…We also found that quercetin induces apoptotic cell death through ER stress in AGS cells based on ROS production and ATF‐6α, ATF‐6β, and GRP‐78 that were the hall markers of ER stress . This is in agreement with other reports which showed that quercetin induced human pancreatic cancer cell death via ER stress mediated apoptotic signaling including reactive oxygen species production and mitochondrial dysfunction . Our earlier studies also showed that quercetin induced cell apoptosis through ER stress in human prostate cancer PC‐3 cells .…”

Anticancer potential of quercetin: A comprehensive review

“…It also increases the buildup of intracellular Ca 2+ ions and Grp78/Bip and GADD153/CCAAT enhancer‐binding protein homologous protein (CHOP) protein expression and triggers mitochondrial dysfunction. Quercetin exerts this cytotoxicity against human pancreatic cancer cells trough endoplasmic reticulum stress‐mediated apoptotic signaling including pathway, as well as ROS production and mitochondrial dysfunction (J. H. Lee et al, ). Other researchers found that quercetin exerts its antiproliferative effects in pancreatic cancer cells by inducing apoptosis and attenuating the growth of orthotopically transplanted pancreatic xenografts (Angst et al, ).…”

Quercetagetin and Patuletin: Antiproliferative, Necrotic and Apoptotic Activity in Tumor Cell Lines

“…We could speculate that the substitution of the –OH group for the methoxyl group in C6 between quercetagetin and patuletin [ 21 ] accounts for this. What has been ascertained is that quercetin is capable of inducing apoptosis [ 36 ]. Our work shows that quercetin, quercetagetin and patuletin all cause significant nuclear fragmentation and have a great capacity to induce caspase-3 activation, sometimes even greater than camptothecin, a well-known inducer of apoptosis [ 37 ].…”