Oridonin induces the apoptosis of metastatic hepatocellular carcinoma cells via a mitochondrial pathway

Zhu,Min; Hong,Dun; Bao,Yanfang; Wang,Chen; Pan,Weibo

doi:10.3892/ol.2013.1541

Oridonin induces the apoptosis of metastatic hepatocellular carcinoma cells via a mitochondrial pathway

Authors:
- Min Zhu
- Dun Hong
- Yanfang Bao
- Chen Wang
- Weibo Pan
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Affiliations: The Public Laboratory, Taizhou Hospital of Zhejiang, Wenzhou Medical College, Linhai, P.R. China, Taizhou Municipal Hospital, Taizhou University Medical School, Taizhou, Zhejiang, P.R. China
Published online on: August 23, 2013 https://doi.org/10.3892/ol.2013.1541
Pages: 1502-1506

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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.

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