Bioactivity and mechanism of jaridonin, a novel ent-kaurene diterpenoid compound, on tumor cells growth in vitro / 中国药学杂志

ABSTRACT

OBJECTIVE: To investigate inhibitory effects of jaridonin, a novel ent-kaurene diterpenoid compound isolated from Isodon rubescens, on human esophageal cancer cells growth in vitro and to understand the possible mechanisms. METHODS: After treatment for 48 h, the potential effect of jaridonin on the cell viability was examined using MTT assay. The effect of jaridonin on cytomorphology was observed by a fluorescence microscopy. The cell cycle distribution and the drop of mitochondrial membrane potential (ΔΦm) of EC-1 cells treated with jaridonin were analyzed by flow cytometry. Expressions of the p53, Bax, p21 and p27 proteins related with mitochondria apoptosis pathways were detected by Western blot. RESULTS: Jaridonin caused strong antiproliferative and apoptotic effects in HeLa, Spc-Al, HT-29, EC-1 cells. Compared with control, treatment with jaridonin induced G2/M phase cell cycle arrest and resulted in a up-regulation of p53. The expression of Bax and p21 as well as p27 is also up-regulated in EC-1 cells treated by jaridonin. Jaridonin promoted the release of cytochrome C from mitochondria to cytosol. The cleavage of caspase-3/9 in EC-1 cells was also observed. CONCLUSION: Jaridonin can significantly inhibit the growth of the cancer cells, and induce the apoptosis. The antitumor activity of jaridonin might be attributed partly to the induction of cell apoptosis through inducing cell cycle arrest and activating mitochondria pathway.