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Quercetin 3-O-glucoside suppresses epidermal growth factor–induced migration by inhibiting EGFR signaling in pancreatic cancer cells

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Tumor Biology

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.

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Acknowledgments

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).

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Authors and Affiliations

  1. Faculty of Biotechnology, College of Applied Life Science, SARI, Jeju National University, 102 Jejudaehak-ro, Jeju-si, Jeju, 690-756, Korea

    Jungwhoi Lee, Song-I Han, Jeong-Hun Yun & Jae Hoon Kim

  2. Subtropical Horticulture Research Institute, Jeju National University, Jeju, 690-756, Korea

    Jae Hoon Kim

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  1. Jungwhoi Lee
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Correspondence to Jae Hoon Kim.

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Lee, J., Han, SI., Yun, JH. et al. Quercetin 3-O-glucoside suppresses epidermal growth factor–induced migration by inhibiting EGFR signaling in pancreatic cancer cells. Tumor Biol. 36, 9385–9393 (2015). https://doi.org/10.1007/s13277-015-3682-x

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  • DOI: https://doi.org/10.1007/s13277-015-3682-x

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