Diosmetin Inhibits Cell Proliferation, Induces Cell Apoptosis and Cell Cycle Arrest in Liver Cancer

摘要

Objective: Diosmetin (DIOS) has been confirmed to possess anti-cancer effects in some types of tumors. However, it remains unclear whether DIOS exerts anti-cancer effects on liver cancer. Thus, our purpose was to observe the effect of DIOS on cell proliferation, cell apoptosis and cell cycle arrest in human liver cancer cells. Materials?and?Methods: The cell viability of HepG2 and HCC-LM3 cells under different concentrations of DIOS was detected using MTT assay. The cell apoptosis and cell cycle arrest were analyzed by flow cytometry. The expression levels of apoptosis/cell cycle-related proteins including P53, Bcl-2, Bax, cleaved-caspase3, cleaved-caspase8, cleaved-PARP, Bak, cdc2, cyclinB1 and P21 were measured using Western blot. HepG2 cells were transfected by checkpoint kinase 1 (Chk1)-small interfering RNA (siRNA) and checkpoint kinase 2 (Chk2)-siRNA, respectively. After that, cell cycle was detected. Results: DIOS significantly suppressed cell proliferation and induced cell apoptosis of HepG2 cells and HCC-LM3 cells. Moreover, DIOS promoted cell cycle arrest in G2/M phase. Western blot results showed that DIOS significantly suppressed the expression levels of Bcl-2, cdc2, cyclinB1, and promoted the expression levels of Bax, cleaved-caspase3, cleaved-caspase8, cleaved-PARP, Bak, P53, and P21. The G2/M phase arrest was observed in HepG2 cells transfected with Chk2-siRNA, while the G2/M phase arrest was not obvious in HepG2 cells transfected with Chk1-siRNA. Conclusion: Our findings revealed that DIOS could inhibit cell proliferation and promote cell apoptosis and cell cycle arrest in liver cancer. Furthermore, DIOS could induce G2/M cell cycle arrest in HepG2 cell via targeting Chk2.