title: Quercetin 3-O-glucoside suppresses epidermal growth factor-induced migration by inhibiting EGFR signaling in pancreatic cancer cells.
abstract: Pancreatic cancer is one of the most dangerous cancers and is associated with a grave prognosis. Despite increased knowledge of the complex signaling networks responsible for progression of pancreatic cancer, many challenging therapies have fallen short of expectations. In this study, we examined the anti-migratory effect of quercetin 3-O-glucoside in epidermal growth factor-induced cell migration by inhibiting EGF receptor (EGFR) signaling in several human pancreatic cancer cell lines. Treatment with quercetin, quercetin 3-O-glucoside, and quercetin 7-O-glucoside differentially suppressed epidermal growth factor-induced migration activity of human pancreatic cancer cells. In particular, quercetin 3-O-glucoside strongly inhibited the infiltration activity of pancreatic cancer cells in a dose-dependent manner. Furthermore, quercetin 3-O-glucoside exerted the anti-migratory effect even at a relatively low dose compared with other forms of quercetin. The anti-tumor effects of quercetin 3-O-glucoside were mediated by selectively inhibiting the EGFR-mediated FAK, AKT, MEK1/2, and ERK1/2 signaling pathway. Combinatorial treatment with quercetin 3-O-glucoside plus gemcitabine showed the synergistic anti-migratory effect on epidermal growth factor-induced cell migration in human pancreatic cancer cell lines. These results suggest that quercetin 3-O-glucoside has potential for anti-metastatic therapy in human pancreatic cancer.
authors.affiliation: Faculty of Biotechnology, College of Applied Life Science, SARI, Jeju National University, 102 Jejudaehak-ro, Jeju-si, Jeju, 690-756, Korea.
authors.forename: Jungwhoi
authors.initials: J
authors.lastname: Lee
authors.affiliation: Faculty of Biotechnology, College of Applied Life Science, SARI, Jeju National University, 102 Jejudaehak-ro, Jeju-si, Jeju, 690-756, Korea.
authors.forename: Song-I
authors.initials: SI
authors.lastname: Han
authors.affiliation: Faculty of Biotechnology, College of Applied Life Science, SARI, Jeju National University, 102 Jejudaehak-ro, Jeju-si, Jeju, 690-756, Korea.
authors.forename: Jeong-Hun
authors.initials: JH
authors.lastname: Yun
authors.affiliation: Faculty of Biotechnology, College of Applied Life Science, SARI, Jeju National University, 102 Jejudaehak-ro, Jeju-si, Jeju, 690-756, Korea. kimjh@jejunu.ac.kr.|Subtropical Horticulture Research Institute, Jeju National University, Jeju, 690-756, Korea. kimjh@jejunu.ac.kr.
authors.forename: Jae Hoon
authors.initials: JH
authors.lastname: Kim
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000235:genetics*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics*; D005419:Flavonoids / Q000008:administration & dosage*; D005960:Glucosides / Q000008:administration & dosage; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D010766:Phosphorylation; D011794:Quercetin / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D005419:Flavonoids; D005960:Glucosides; C532085:quercetin 3'-O-glucoside; C089996:quercimeritrin; D004815:Epidermal Growth Factor; D011794:Quercetin; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: EGF; EGFR; ERK/1/2; FAK; Migration; Pancreatic cancers; Quercetin; Quercetin-3-O-glucoside