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Chrysin inhibits sphere formation in SMMC-7721 cells via modulation of SHP-1/STAT3 signaling pathway
Yanqin Zhang1,2, Feng Chen1, Xinghua Xiao1
1Department of Pharmacy, Xiangya Hospital of Central South University, Changsha, 410008, People's Republic of China.
Abstract:
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.
Insights
Chrysin, a natural flavonoid, inhibits hepatocellular carcinoma (HCC) sphere formation by upregulating SHP-1 protein and modulating the SHP-1/STAT3 pathway, offering potential anti-cancer effects.
Area of Science:
- Biochemistry
- Oncology
- Molecular Biology
Background:
- Chrysin, a natural flavonoid, exhibits anti-cancer properties against various cancer cells.
- Chrysin has shown potential in inhibiting sphere formation in hepatocellular carcinoma (HCC) cell lines.
- The precise mechanism of chrysin's action on HCC spheres is not fully understood.
Purpose of the Study:
- To investigate the effect of chrysin on SHP-1 and STAT3 signaling in HCC.
- To elucidate the mechanism by which chrysin inhibits HCC sphere formation.
Main Methods:
- Investigated SHP-1 protein expression in HCC spheres.
- Assessed the impact of chrysin on SHP-1, p-STAT3, and Twist1 expression.
- Utilized SHP-1 knockdown to validate its role in chrysin's anti-sphere formation effects.
Main Results:
- SHP-1 protein expression was decreased in HCC spheres.
- Chrysin treatment significantly inhibited sphere formation and increased SHP-1 levels.
- Chrysin reduced p-STAT3 and Twist1 expression; SHP-1 knockdown reversed these effects and chrysin's inhibition of sphere formation.
Conclusions:
- Chrysin effectively inhibits HCC sphere formation.
- The mechanism involves the modulation of the SHP-1/STAT3 signaling pathway.
- Chrysin shows promise as a therapeutic candidate for HCC treatment.
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