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.
Hepatoid adenocarcinomas of the stomach are gastric carcinomas with both adenocarcinomatous and hepatocellular differentiations. The tumor was characterized by high serum alpha-fetoprotein (AFP) levels. A 73-year-old male patient was admitted to the hospital with abdominal pain. Gastrofiberscopy revealed a gastric tumor occupying the antrum and pylorus. Radical subtotal gastrectomy was done and the result of biopsy was poorly differentiated adenocarcima of stomach and stage 3B. At postoperation 8 month, AFP was elevated and liver mass was detected on CT. Right extended hepatectomy was done under the impression of primary liver tumor. But, the biopsy revealed metastatic hepatoid adenocarcinoma of the stomach. Re-examination of the resected stomach was done and the result was hepatoid adenocarcinoma of the stomach. Two months later, after the hepatic resection, multiple metastases developed. This type of tumor has frequent early liver metastasis and poor prognosis. Therefore, early diagnosis and more careful investigation for liver metastasis are recommended.
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