Flavonoids luteolin and quercetin can inhibit growth and metastasis of cancer cells. In our previous report, luteolin and quercetin was shown to block Akt/mTOR/c-Myc signaling. Here, we found luteolin and quercetin reduced protein level and transactivation activity of RPS19 in A431-III cells, which is isolated from parental A431 (A431-P) cell line. Further investigation the inhibitory mechanism of luteolin and quercetin on RPS19, we found c-Myc binding sites on RPS19 promoter. The Akt inhibitor LY294002, mTOR inhibitor rapamycin and c-Myc inhibitor 10058-F4 significantly suppressed RPS19 expression and transactivation activities. Overexpression and knockdown of c-Myc in cancer cells show RPS19 expression was regulated by c-Myc. Furthermore, Knockdown and overexpression of RPS19 was used to analyze of the function of RPS19 in cancer cells. The epithelial-mesenchymal transition (EMT) markers and metastasis abilities of cancer cells were also regulated by RPS19. These data suggest that luteolin and quercetin might inhibit metastasis of cancer cells by blocking Akt/mTOR/c-Myc signaling pathway to suppress RPS19-activated EMT signaling.

中文翻译：

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类黄酮木犀草素和槲皮素抑制 RPS19 并通过减少 c-Myc 促进癌细胞的转移

黄酮类木犀草素和槲皮素可以抑制癌细胞的生长和转移。在我们之前的报告中，木犀草素和槲皮素被证明可以阻断 Akt/mTOR/c-Myc 信号传导。在这里，我们发现木犀草素和槲皮素降低了从亲代 A431 (A431-P) 细胞系中分离的 A431-III 细胞中 RPS19 的蛋白质水平和反式激活活性。进一步研究木犀草素和槲皮素对RPS19的抑制机制，我们在RPS19启动子上发现了c-Myc结合位点。Akt 抑制剂 LY294002、mTOR 抑制剂雷帕霉素和 c-Myc 抑制剂 10058-F4 显着抑制 RPS19 表达和反式激活活性。癌细胞中 c-Myc 的过表达和敲低显示 RPS19 表达受 c-Myc 调节。此外，使用 RPS19 的敲低和过表达来分析 RPS19 在癌细胞中的功能。癌细胞的上皮间质转化 (EMT) 标志物和转移能力也受 RPS19 的调节。这些数据表明，木犀草素和槲皮素可能通过阻断 Akt/mTOR/c-Myc 信号通路抑制 RPS19 激活的 EMT 信号通路来抑制癌细胞的转移。