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Quercetin Suppresses CYR61-Mediated Multidrug Resistance in Human Gastric Adenocarcinoma AGS Cells

Faculty of Biotechnology, College of Applied Life Sciences, SARI, Jeju National University, Jeju 63243, Korea
Subtropical/Tropical Organism Gene Bank, Jeju National University, Jeju 63243, Korea
Faculty of Advanced Convergence Technology & Science, Jeju National University, Jeju 63243, Korea
Author to whom correspondence should be addressed.
Molecules 2018, 23(2), 209;
Received: 20 December 2017 / Revised: 20 January 2018 / Accepted: 24 January 2018 / Published: 24 January 2018
(This article belongs to the Collection Herbal Medicine Research)
PDF [2624 KB, uploaded 24 January 2018]


Cysteine-rich angiogenic inducer 61 (CYR61) is an extracellular matrix-associated protein involved in survival, tumorigenesis, and drug resistance. Therefore, we examined the effects of flavones against CYR61-overexpressing human gastric adenocarcinoma AGS (AGS-cyr61) cells, which show remarkable resistance to 5-fluorouracil (5-FU), adriamycin (ADR), tamoxifen (TAM), paclitaxel (PAC), and docetaxel (DOC). Among the tested flavones, quercetin had the lowest 50% inhibitory concentration (IC50) and significantly reduced the viability of AGS-cyr61 cells compared with AGS cells. Quercetin: (1) reduced multidrug resistance-associated protein 1 and nuclear factor (NF)-kappa B p65 subunit levels; (2) reversed multidrug resistance (MDR); (3) inhibited colony formation and induced caspase-dependent apoptosis; and (4) suppressed migration and down-regulated epithelial–mesenchymal transition-related proteins in AGS-cyr61. Moreover, AGS-cyr61 cells treated with quercetin concentrations close to the IC50 and simultaneously treated with 5-FU or ADR in the sub-lethal range showed strong synergism between quercetin and these two drugs. These findings indicate that CYR61 is a potential regulator of drug resistance and that quercetin may be a novel agent for improving the efficacy of anticancer drugs in AGS-cyr61 cells. View Full-Text
Keywords: apoptosis; CYR61; multidrug resistance (MDR); quercetin; synergistic effect apoptosis; CYR61; multidrug resistance (MDR); quercetin; synergistic effect

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Hyun, H.B.; Moon, J.Y.; Cho, S.K. Quercetin Suppresses CYR61-Mediated Multidrug Resistance in Human Gastric Adenocarcinoma AGS Cells. Molecules 2018, 23, 209.

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