title: Quercetin aglycone is bioavailable in murine pancreas and pancreatic xenografts.
abstract: Quercetin is a potential chemopreventive and chemotherapeutic agent for pancreatic and other cancers. This study examined 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 a cellular in vitro model. Mice were randomly allocated to control or 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 the chemotherapeutic drug gemcitabine (120 mg/kg mouse, ip). MiaPaCa cells were collected from culture medium after cells were exposed to 30 muM quercetin for 0.5, 1, 2, 4, 8, and 24 h. Levels of quercetin and 3-O'-methylquercetin in mouse tissues and MiaPaCa-2 cells were measured by high-pressure liquid chromatography following enzymatic hydrolysis and then extraction. The 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 is aglycones. Gemcitabine cotreatment with quercetin reduced absorption of quercetin in the mouse circulatory system and liver. Results from the study provide important information on the interpretation of the chemotherapeutic efficacy of quercetin.
authors.affiliation: Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA.
authors.forename: Lifeng
authors.initials: L
authors.lastname: Zhang
authors.forename: Eliane
authors.initials: E
authors.lastname: Angst
authors.forename: Jenny L
authors.initials: JL
authors.lastname: Park
authors.forename: Aune
authors.initials: A
authors.lastname: Moro
authors.forename: David W
authors.initials: DW
authors.lastname: Dawson
authors.forename: Howard A
authors.initials: HA
authors.lastname: Reber
authors.forename: Guido
authors.initials: G
authors.lastname: Eibl
authors.forename: O Joe
authors.initials: OJ
authors.lastname: Hines
authors.forename: Vay-Liang W
authors.initials: VL
authors.lastname: Go
authors.forename: Qing-Yi
authors.initials: QY
authors.lastname: Lu
mesh_terms: D000818:Animals; D001682:Biological Availability; D045744:Cell Line, Tumor; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D010179:Pancreas / Q000737:chemistry / Q000187:drug effects*; D010190:Pancreatic Neoplasms / Q000737:chemistry / Q000188:drug therapy*; D011794:Quercetin / Q000008:administration & dosage / Q000032:analysis* / Q000493:pharmacokinetics*; D011897:Random Allocation; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D011794:Quercetin