Germacrone induces apoptosis in human hepatoma HepG2 cells through inhibition of the JAK2/STAT3 signalling pathway.

Abstract

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 Western 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 germacrone for 24 h. The expression of p-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.

• Authors: Yun-Yi Liu, Qian Zheng, Bin Fang, Wei Wang, Feng-Yun Ma, Sadia Roshan, Amal Banafa, Ming-Jie Chen, Jun-Li Chang, Xiao-Min Deng, Ke-Xiu Li, Guang-Xiao Yang, Guang-Yuan He
• Journal: Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban (J Huazhong Univ Sci Technolog Med Sci) Vol. 33 Issue 3 Pg. 339-345 (Jun 2013) ISSN: 1672-0733 [Print] China
• PMID: 23771657 (Publication Type: Journal Article)

Chemical References

• Drugs, Chinese Herbal
• STAT3 Transcription Factor
• STAT3 protein, human
• Sesquiterpenes, Germacrane
• germacrone
• JAK2 protein, human
• Janus Kinase 2

Topics

• Apoptosis (drug effects)
• Dose-Response Relationship, Drug
• Drugs, Chinese Herbal (administration & dosage)
• Hep G2 Cells
• Humans
• Janus Kinase 2 (metabolism)
• STAT3 Transcription Factor (metabolism)
• Sesquiterpenes, Germacrane (administration & dosage)
• Signal Transduction (drug effects)