Abstract 4179: Quercetin inhibits growth of pancreatic cancer in vitro and in vivo

Abstract

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.

Quercetin Aglycone Is Bioavailable in Murine Pancreas and Pancreatic Xenografts

“…As quercetin is eliminated mainly in bile, its levels in pancreas and liver generate high concentration variation. It is important to note that quercetin (1%) co-treatment with gemcitabine significantly inhibit the growth of tumor in orthotopic murine model(39). Our data provided important information on the therapeutic efficacy of quercetin.…”