Bavachalcone from Cullen corylifolium induces apoptosis and autophagy in HepG2 cells.

BACKGROUND: Cullen corylifolium is a plant widely used in traditional Chinese medicine for its stomachic, anthelmintic, and diuretic properties. Bavachalcone, which is known as a component of C. corylifolium has been reported to inhibit osteoclast differentiation. However, the anticancer efficacy and mechanism of C. corylifolium and bavachalcone have not been studied.

HYPOTHESIS/PURPOSE: Our aim is to determine whether C. corylifolium has an anticancer effect and to identify the apoptosis and autophagy mechanism of bavachalcone.

STUDY DESIGN/METHOD: The anti-proliferative activity of C. corylifolium and bavachalcone was measured with MTT assay. Apoptosis was analyzed using Annexin V and propidium iodide staining. The expression of apoptosis, cell cycle and autophagy related gene was evaluated by western blot. Cell cycle stage was investigated with TaliⓇ image-based cytometer. Autophagic activity was assessed using monodansylcadaverine (MDC) staining.

RESULT: C. corylifolium exhibited potent effect on apoptosis in HepG2 cells. To identify which compound in C. corylifolium is responsible for this effect, we determined the effects of psoralen, psoralidin, bavachalcone, and isobavachalcone on the activity of bid, caspase 3, and PARP. Of all the studied compounds, bavachalcone was the most potent inducer of apoptosis and acted via crosstalk between the intrinsic and extrinsic pathways. In addition, bavachalcone caused cell cycle arrest and decreased the levels of early cell cycle regulatory proteins such as CDK 4 and CDK 2, whereas p21 and p27 levels were increased. We also investigated the extent to which bavachalcone-induced autophagy and apoptosis were related. Phosphorylation and expression of Akt and mTOR were decreased, while the LC3 Ⅱ to LC3Ⅰ ratio was increased in bavachalcone-treated cells. These results suggest that bavachalcone has anticancer activity by promoting both autophagy and apoptosis in HepG2 cells.

CONCLUSION: C. corylifolium has an anticancer effect. Especially, bavachalcone has excellent anticancer ability among other components of C. corylifolium by inducing apoptosis and autophagy.