title: Oridonin induces the apoptosis of metastatic hepatocellular carcinoma cells via a mitochondrial pathway.
abstract: The selective induction of apoptosis is a promising strategy for cancer therapy. The antitumor effects of oridonin have been reported in several types of malignant tumors. However, the effects of oridonin on MHCC97-H cells, a highly metastatic human hepatocellular carcinoma cell line, have not been reported. The present study aimed to determine the effect of oridonin on the apoptosis of MHCC97-H cells and to identify the underlying molecular mechanisms that are involved. Compared with the untreated control cells, oridonin significantly decreased (P<0.05) cell proliferation in a concentration- and time-dependent manner. Oridonin at concentrations of 12.5, 25, 50 and 100 μM resulted in increased apoptotic Annexin V-positive and propidium iodide-negative cells by 9.5, 15.6, 22.2 and 31.7%, respectively, compared with the control groups (P<0.05). The mitochondrial membrane potential was significantly decreased by 6.0, 12.9, 18.9 and 27.1% in the MHCC97-H cells that were treated with oridonin at concentrations of 12.5, 25, 50 and 100 μM, respectively, for 24 h compared with the control groups (P<0.05). Oridonin increased the activity of caspase-3 and the expression of cleaved caspase-9 and cytochrome c in the cytoplasm and decreased the Bcl-2:Bax ratio in a concentration-dependent manner. The data indicate that oridonin inhibited the proliferation of the MHCC97-H cells by inducing apoptosis via a mitochondrial pathway. This mitochondrial pathway of apoptosis involved a reduction in the mitochondrial membrane potential and the subsequent release of cytochrome c and activation of caspase-3 and -9.
authors.affiliation: The Public Laboratory, Taizhou Hospital of Zhejiang, Wenzhou Medical College, Linhai, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhu
authors.forename: Dun
authors.initials: D
authors.lastname: Hong
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Bao
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.forename: Weibo
authors.initials: W
authors.lastname: Pan
keywords: MHCC97-H cells; apoptosis; mitochondrial pathway; oridonin