Antiproliferative effect and mechanism of rocaglaol on HepG2 cells / 中草药

ABSTRACT

Objective: To study the effect of rocaglaol from Aglaia odorata on HepG2 proliferation and to explore the potential anti-tumor mechanism. Methods: The MTT, colony formation, EdU incorporation, and CFDA-SE assays were used to determine the anti-proliferative activity of rocaglaol in HepG2 cells. Apoptosis and cell cycle distribution effect induced by rocaglaol were carried out by flow cytometry. The effect of rocaglaol on protein involved in the G2/M checkpoint and the MAPK pathway were performed by Western blotting analysis. Results: Rocaglaol significantly inhibited the viability of HepG2 cells in a dose-dependent and time-dependent manner. Rocaglaol was more effective than doxorubicin in the growth inhibition of HepG2 cells. However, rocaglaol-induced cytotoxicity in normal human hepatic cell line L02 was lower than that of doxorubicin. Treatment with different concentrations of rocaglaol at 48 h caused G2/M cell cycle progression inhibition, rather than apoptosis in HepG2 cells. Rocaglaol can significantly reduce the expression of G2/M cell cycle-regulating proteins cdc25C, cdc2, and cyclin B1 as well as increase the expression of ERK and JNK phosphorylation levels. Further study found that U0126 can partly abrogate the anti-proliferative activity in HepG2 cells, G2/M phase arrest and the reduction in the protein expression levels of cdc2 and cdc25C induced by rocaglaol. Conclusion: Our results demonstrated that rocaglaol was superior to doxorubicin in the inhibition of HepG2 cells proliferation and the selectivity of L02 cell activity. We provided evidence that the rocaglaol had the ability to continuously over-activate the ERK signaling in HepG2 cells, leading to the inhibition of cell proliferation through G2/M phase arrest.