Proteomic and functional analyses demonstrate the involvement of oxidative stress in the anticancer activities of oridonin in HepG2 cells
Oridonin exhibits a curative effect on liver carcinoma in patients and experimental animals. In the present study, we performed proteomic and functional analyses to explore the mechanism involved in the anticancer activity of oridonin. Oridonin treatment for 24 h resulted in a
dose-dependent decrease in cell viability with an IC50 value of 37.90 µM. Treatment with 40 µM oridonin for 24 h induced apoptosis as typical apoptotic nuclear alterations were observed following DAPI staining. Using a 2-DE-based proteomic approach, 3 upregulated oxidative
stress markers, Hsp70-1, Hop and Prdx2, were identified in the HepG2 cells treated with 40 µM oridonin for 24 h. A pattern of alteration in Hsp70-1 was verified by western blotting. The mRNA expression patterns of Hsp70-1 and Hop as determined by qPCR were comparable to their
protein expression patterns. Further investigations showed that oridonin treatment for 24 h resulted in reactive oxygen species (ROS) generation, and ROS scavenger N-acetylcysteine (NAC) completely inhibited ROS production and restored cell viability, suggesting that oxidative stress
contributed to oridonin-induced HepG2 cell death. Western blot analysis of oxidative stress pathway-related proteins demonstrated that oridonin treatment increased p-JNK, p-p38 and p-p53, and decreased Bcl-2 protein expression levels, promoted cytochrome c release, decreased mitochondrial
membrane potential, and activated caspase-9 and caspase-3. Furthermore, knockdown of Hsp70-1 expression with specific shRNA significantly decreased the viability of the cells treated with oridonin, suggesting a protective role of Hsp70-1 in oridonin-mediated oxidative stress. The results of
the present study provide evidence for a link between oxidative stress and oridonin-induced apoptosis in HepG2 cells.
Document Type: Research Article
Affiliations: 1: Guangdong Provincial Key Laboratory of Biotechnology Candidate Drug Research, School of Life Science and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou, P.R. China 2: Center for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, SAR, P.R. China
Publication date: 01 January 2014
- Oncology Reports is a monthly, peer-reviewed journal devoted to the publication of high quality original studies and reviews concerning a broad and comprehensive view of fundamental and applied research in oncology, focusing on carcinogenesis, metastasis and epidemiology.
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