Costunolide isolated from Vladimiria souliei inhibits the proliferation and induces the apoptosis of HepG2 cells

Abstract

Costunolide (cos) is one of the major sesquiterpenes isolated from the ethyl acetate soluble fraction of the roots of Vladimiria souliei. In order to explore the effects and molecular mechanism of cos, the anti-proliferative and apoptotic effects of cos against the human hepatoblastoma HepG2 cell line was examined in vitro in the current study. Cell viability was measured using an MTT assay, and IC50 values (indicating the concentration required to achieve half-maximal inhibition) were calculated to detect the inhibitory effect of cos on HepG2 cell growth. Cell morphology was subsequently observed under an inverted microscope, and cell cycle distribution and apoptosis were detected using flow cytometric analysis. In addition, changes in the protein expression levels of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), and caspases-3, -8 and -9 were detected by western blotting. The results of cell analyses indicated that cos treatment inhibited the proliferation and promoted the apoptosis of HepG2 cells in vitro. Cos markedly induced HepG2 cell apoptosis by arresting the cell cycle at the G2/M phase in a dose-dependent manner. In terms of the underlying mechanism, cos was revealed to inhibit the anti-apoptotic capacity of the cells, possibly via upregulating the expression levels of Bax protein and caspases-3, -8 and -9, and downregulating the expression of Bcl-2 protein. Taken together, the results of the present study indicate that cos may be a promising candidate for liver cancer therapy, and have provided an insight into the mechanism of action involved in its anti-cancer properties.