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Molecules 2018, 23(2), 209; https://doi.org/10.3390/molecules23020209

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

1
Faculty of Biotechnology, College of Applied Life Sciences, SARI, Jeju National University, Jeju 63243, Korea
2
Subtropical/Tropical Organism Gene Bank, Jeju National University, Jeju 63243, Korea
3
Faculty of Advanced Convergence Technology & Science, Jeju National University, Jeju 63243, Korea
*
Author to whom correspondence should be addressed.
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)
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Abstract

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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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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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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