There is an increasing demand for agents that target cysteine-rich angiogenic inducer 61 (CYR61), 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, paclitaxel, and docetaxel. Among the tested flavones, quercetin had the lowest 50% inhibitory concentration (IC<sub>50</sub>) 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, (3) inhibited colony formation and induced caspase-dependent apoptosis, and (4) suppressed migration and downregulated epithelial–mesenchymal transition-related proteins in AGS-cyr61. Moreover, AGS-cyr61 cells treated with quercetin concentrations close to the IC<sub>50</sub> 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.

Effect of quercetin on the inhibition of CYR61-mediated multidrug resistance in human adenocarcinoma AGS cells

256th National Meeting (2018)

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