Chrysin inhibits sphere formation in SMMC-7721 cells via modulation of SHP-1/STAT3 signaling pathway

Background: Chrysin is a natural flavonoid which has been identified as a candidate anti-cancer agent due to its inhibitory effect on a variety of cancer cells, including targeted inhibition of sphere formation in hepatocellular carcinoma (HCC) cell lines. However, the mechanism by which chrysin modulates HCC spheres remains unclear. Materials and methods: In this study, we investigate the effect of chrysin on the regulation of SHP-1 and its downstream signal molecule STAT3 to explain the mechanism by which chrysin inhibits sphere formation of HCC cell lines. Results: Here, we found that SHP-1 protein expression was markedly down-regulated in the spheres from both SMMC-7721 and MHCC97H cells. Chrysin significantly inhibited sphere formation and upregulated the expression of SHP-1 protein in both SMMC-7721 and MHCC97H cells, as well as reduced p-STAT3 and Twist1 expressions in SMMC-7721 cells. Furthermore, knockdown of SHP-1 in SMMC-7721 cells resulted in the induction of p-STAT3 and Twist1 protein expression and antagonizing the inhibitory effect of chrysin on sphere formation in SMMC-7721 cells. Conclusion: Overall, the study findings demonstrated that chrysin acts as a candidate for the treatment of HCC through modulating SHP-1/STAT3 signaling pathway.