AIM Reeently, we isolated a novel ent-kaurene diterpenoid compound, from Isodon rubescens, named Jaridonin.The current study is designed to determine the cytotoxic effects of the new compound on human esophageal cancer cells and the underlying mechanisms.METHODS MTT assay was used to evaluate the cell viability.Cell morphology was observed and mitochondrial membrane potential was measured through a fluorescence microscopy.Cell apoptosis, cell cycle distribution and the value of mitochondrial membrane potential (△tΨm) were analyzed by flow cytometry.Intracellular levels of hydrogen peroxide or superoxide were determined by the redox-sensitive probes 2, 7-dichlorodihydrofluorescein diacetate (DCFH-DA) or dihydroethidium (DHE).Expression of the related proteins in mitochondrial apaptotic pathways, including: P53, Bax, p21, cleaved caspase 9 and caspase 3, were detected by Western blot.RESULTS Compared with controls, Jaridonin caused strong antiproliferative and apoptotic effects in HeLa, Spc-A1,HT-29, EC-1 cells and induced G2/M phase cell cycle arrest in EC1 cells.Jaridonin also resulted in a significant loss of mitochondrial membrane potential, release of cytochrome c into the cytosol and activation of caspase 9 and caspase 3.These cytotoxic effects of Jaridonin were associated with marked accumulation of reactive oxygen species (ROS) and increased expression of p53, p21wafl/cipl and Bax, whereas a ROS scavenger, N-acetyl-L-cysteine (L-NAC), significantly attenuated the effects of Jaridonin on the mitochondrial membrane potential, DNA damage, the expressions of p53 and p21 waf1/Cip1 and cell viabilities.CONCLUSION Jaridonin inhibits the cancer cell growth and induces apoptosis, which may be related to the induction of cell apoptosis through cell cycle arrest and activating ROS-dependent mitochondrial cell death pathway.