Quercetin 3-O-glucoside suppresses epidermal growth factor–induced migration by inhibiting EGFR signaling in pancreatic cancer cells
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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.
KeywordsQuercetin Quercetin-3-O-glucoside EGF EGFR FAK ERK/1/2 Migration Pancreatic cancers
This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2009-0094059).
Conflicts of interest
- 1.Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA: Cancer J Clin. 2014;64:9–29.Google Scholar
- 18.Korc M, Chandrasekar B, Yamanaka Y, Friess H, Buchier M, Beger HG. Overexpression of the epidermal growth factor receptor in human pancreatic cancer is associated with concomitant increases in the levels of epidermal growth factor and transforming growth factor alpha. J Clin Investig. 1992;90:1352–60.CrossRefPubMedPubMedCentralGoogle Scholar
- 26.Moore MJ, Goldstein D, Hamm J, Figer A, Hecht JR, Gallinger S, et al. Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer: a phase iii trial of the national cancer institute of canada clinical trials group. J Clin Oncol : Off J Am Soc Clin Oncol. 2007;25:1960–6.CrossRefGoogle Scholar
- 29.Aranda E, Manzano JL, Rivera F, Galan M, Valladares-Ayerbes M, Pericay C, et al. Phase ii open-label study of erlotinib in combination with gemcitabine in unresectable and/or metastatic adenocarcinoma of the pancreas: relationship between skin rash and survival (pantar study). Ann Oncol : Off J Europ Soc Med Oncol/ESMO. 2012;23:1919–25.CrossRefGoogle Scholar