Germacrone Induces Apoptosis in Human Hepatoma HepG2 Cells through Inhibition of the JAK2/STAT3 Signalling Pathway

• Published in: Journal of Huazhong University of Science and Technology. Medical sciences Vol. 33; no. 3; pp. 339 - 345
• Main Author: 柳昀熠 郑倩 方斌 王维 马凤云 Sadia Roshan Amal Banafa 陈明洁 常俊丽 邓小敏 李克秀 杨广笑 何光源
• Format: Journal Article
• Language: English
• Published: Heidelberg Huazhong University of Science and Technology 01.06.2013; The Genetic Engineering International Cooperation Base of Chinese Ministry of Science and Technology, Chinese National Center of Plant Gene Research(Wuhan)HUST Part, Key Laboratory of Molecular Biophysics of Chinese Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China
• Subjects: Apoptosis - drug effects; Bcl-2家族; Dose-Response Relationship, Drug; Drugs, Chinese Herbal - administration & dosage; Hep G2 Cells; HepG2细胞; Humans; Janus Kinase 2 - metabolism; Medicine; Medicine & Public Health; RT-PCR检测; Sesquiterpenes, Germacrane - administration & dosage; Signal Transduction - drug effects; STAT3; STAT3 Transcription Factor - metabolism; Western印迹; 信号通路; 细胞凋亡; 诱导; JAK2/STAT3; apoptosis; HepG2 cells; germacrone
• ISSN: 1672-0733; 1993-1352
• DOI: 10.1007/s11596-013-1121-z

Summary： Previous studies have shown that STAT3 plays a vital role in the genesis and progression of cancer. In this study, we investigated the relationship between the JAK2/STAT3 signalling pathway and germacrone-induced apoptosis in HepG2 cells. HepG2 cells were incubated with germacrone for 24 h, the protein expression of p-STAT3, STAT3, p-JAK2 and JAK2 was detected by Westem Blotting, and RT-PCR was used to determine the expression of STAT3, p53, Bcl-2 and Bax at transcriptional levels. Besides that, HepG2 cells were pre-treated with AG490 or IL-6 for 2 h, and then incubated with ger- macrone for 24 h. The expression ofp-JAK2, JAK2, p-STAT3, STAT3, p53, Bax and Bcl-2 was detected by Western blotting. The activity of HepG2 cells was tested by MTT assay. The apoptosis of HepG2 cells and levels of reactive oxygen species （ROS） were flow cytometrically measured. The results showed that germacrone exposure decreased p-STAT3 and p-JAK2 and regulated expression of p53 and Bcl-2 family members at the same time. Moreover, IL-6 enhanced the activation of the JAK2/STAT3 signalling pathway and therefore attenuated the germacrone-induced apoptosis. Suppression of JAK2/STAT3 signalling pathway by AG490, an inhibitor of JAK2, resulted in apoptosis and an increase in ROS in response to germacrone exposure. We therefore conclude that germacrone induces apoptosis through the JAK2/STAT3 signalling pathway.