Flavonoids Luteolin and Quercetin Inhibit RPS19 and contributes to metastasis of cancer cells through c-Myc reduction

Flavonoids luteolin and quercetin can inhibit growth and metastasis of cancer cells. In ourprevious 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 ofRPS19 in A431-III cells, which is isolated from parental A431 (A431-P) cell line. Furtherinvestigation the inhibitory mechanism of luteolin and quercetin on RPS19, we found c-Myc binding sites on RPS19 promoter. The Akt inhibitor LY294002, mTOR inhibitor rapamycinand c-Myc inhibitor 10058-F4 significantly suppressed RPS19 expression andtransactivation activities. Overexpression and knockdown of c-Myc in cancer cells showRPS19 expression was regulated by c-Myc. Furthermore, Knockdown and overexpression ofRPS19 was used to analyze of the function of RPS19 in cancer cells. The epithelialmesenchymaltransition (EMT) markers and metastasis abilities of cancer cells were alsoregulated by RPS19. These data suggest that luteolin and quercetin might inhibit metastasisof cancer cells by blocking Akt/mTOR/c-Myc signaling pathway to suppress RPS19-activated EMT signaling.