Objectives The flavonoid quercetin holds promise as an anti-tumor agent in several preclinical animal models. However, the efficacy of oral administration of quercetin in a pancreatic cancer mouse model is unknown. Methods The anti-proliferative effects of quercetin alone or in combination with gemcitabine were tested in two human pancreatic cancer cell lines using cell count and MTT assays. Apoptosis was evaluated by flow cytometry. Tumor growth in vivo was investigated in an orthotopic pancreatic cancer animal model using bioluminescence. Quercetin was administered orally in the diet. Results Quercetin inhibited the growth of pancreatic cancer cell lines, which was caused by an induction of apoptosis. In addition, dietary supplementation of quercetin attenuated the growth of orthotopically transplanted pancreatic xenografts. The combination of gemcitabine and quercetin had no additional effect compared to quercetin alone. In vivo quercetin caused significant apoptosis and reduced tumor cell proliferation. Conclusions Our data provide evidence that oral administration of quercetin was capable of inhibiting growth of orthotopic pancreatic tumors in a nude mouse model. These data suggest a possible benefit of quercetin in patients with pancreatic cancer.

Quercetin is a potential chemopreventive and chemotherapeutic agent for pancreatic and other cancers. This study was to examine the distribution of quercetin in plasma, lung, liver, pancreas and pancreatic cancer xenografts in a murine in vivo model and the uptake of quercetin in pancreatic cancer MiaPaCa-2 cells in cellular in vitro model. Mice were randomly allocated to control diet, 0.2 and 1% quercetin diet groups utilizing the AIN93G-based diet (n=12 per group) for 6 weeks. In addition, 6 mice from each group were injected weekly with chemotherapeutic drug gemcitabine (120 mg/kg mouse, i.p.). MiaPaCa cells were collected from culture medium after cells were exposed to 30 µM of quercetin for 0.5, 1, 2, 4, 8, and 24 hrs. Levels of quercetin and 3-O'-methyl-quercetin in mice tissues and MiaPaCa-2 cells were measured by high-pressure liquid chromatography following enzymatic hydrolysis and then extraction. Our study showed that quercetin is accumulated in pancreatic cancer cells, and is absorbed in the circulating system, tumors and tissues of pancreas, liver and lung in vivo. A higher proportion of total quercetin found in tumors and pancreas are aglycones. Gemcitabine co-treatment with quercetin reduced absorption of quercetin in mice circulatory system and liver. Results from the study provide important information on the interpretation of chemo-therapeutic efficacy of quercetin.

Background and Aim: Polyphenols are common constituents of many fruits and vegetables, and have recently gained interest as potential therapeutic agents for various human malignancies. The most abundant of these polyphenols are flavonoids - quercetin being the most ubiquitous. The aim of this study was to assess the growth-inhibitory and anti-angiogenic properties of quercetin on pancreatic cancer (PaCa) cells in vitro and in vivo. Methods and Results: Using cell count and BrdU assay, we measured a dose-dependent inhibition of cell proliferation by quercetin (0-75µM) for MIA PaCa-2 (MP) and BxPC-3 (Bx) cells (p<0.001 at 30µM). Quercetin (10 µM) increased apoptosis by 22% and 8% in MP and Bx, respectively (p<0.05). Further, quercetin (10 µM) inhibited mRNA and protein expression of the pro-angiogenic chemokine CXCL8 (p<0.05) in both cell lines as measured by ELISA and real-time PCR. Conditioned media from PaCa cells treated with 50 µM quercetin reduced endothelial cell tube formation by ∼50% compared to control (p<0.05). A feeding study was conducted utilizing an orthotopic xenograft model of PaCa in nude mice. Luciferase-expressing MP (3×106) cells were injected subcutaneously into the flank of donor mice. After four weeks, 1 mm3 donor tumor sections were transplanted into the pancreatic tail of recipient mice. These animals were randomly allocated to control diet or 1% quercetin diet groups utilizing the AIN93G-based diet (n=12 per group). In addition, 6 mice from each group were injected weekly with gemcitabine (120 mg/kg mouse, i.p.). Animals were imaged weekly after tumor implantation until sacrifice at 6 weeks. Light emission was reduced in animals receiving quercetin, gemcitabine, and both treatments by 12%, 8%, and 16%, respectively at day 24. Furthermore, CXCL8 serum levels were significantly reduced in the quercetin/gemcitabine group (p<0.001). Using HPLC analysis, quercetin and its metabolite, isorhamnetin, were detected in tumor tissues (2.6 ± 2.7 and 2.1 ± 0.9 nmol/gram, respectively). Conclusion: Quercetin significantly inhibits the growth of PaCa in vitro and in an orthotopic murine model. PaCa growth was inhibited utilizing a bioavailable quercetin preparation in the diet. Quercetin may, in part, be acting through a reduction of angiogenesis. From this data we surmise that quercetin may be useful as an adjunct to current treatment for pancreatic cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4179.

No abstract

No abstract