quercetin-3--o-beta-d-glucopyranoside and Pancreatic-Neoplasms

Analysis using Universal exPress Codes (UPCs) with the public microarray database GEO indicates significantly higher mRNA expressions of VEGF-A, bFGF, and bFGFR2 in pancreatic cancers than those in normal pancreatic tissues. Human pancreatic cancer cell line CFPAC-1 and SNU-213 had relatively differential sensitivity to exogenous VEGF-A, bFGF, and TGF-β1 in migration property. Treatment of quercetin-3-O-glucoside suppressed the migratory activity induced by TGF-β and VEGF-A even at relatively low dosages in CFPAC-1, but not in bFGF-activated SNU-213 cells. However, high dosages of quercetin-3-O-glucoside sufficiently suppressed the migratory activity induced by bFGF in SNU-213 cells. Furthermore, co-treatment with low dose of gemcitabine plus quercetin-3-O-glucoside showed synergistic inhibition effects on the infiltrate activity induced by bFGF in CFPAC-1 and SNU-213 cells. These results collectively suggested that quercetin-3-O glucoside could act as an inhibitor of local metastasis induced by various growth factors in pancreatic cancers and be an effective adjuvant to boost chemotherapeutic efficacy of gemcitabine, currently used in pancreatic cancers.

Topics: Cell Line, Tumor; Cell Movement; Databases, Genetic; Deoxycytidine; Dose-Response Relationship, Drug; Drug Synergism; Fibroblast Growth Factor 2; Flavonoids; Gemcitabine; Gene Expression Regulation, Neoplastic; Glucosides; Humans; In Vitro Techniques; Pancreatic Neoplasms; Quercetin; Transforming Growth Factor beta; Vascular Endothelial Growth Factor A

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.

Topics: Apoptosis; Cell Line, Tumor; Cell Movement; Epidermal Growth Factor; ErbB Receptors; Flavonoids; Glucosides; Humans; MAP Kinase Signaling System; Pancreatic Neoplasms; Phosphorylation; Quercetin